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- Classification Summary
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- Germline
- Conditions
- Submissions
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NM_015192.4(PLCB1):c.3128C>T (p.Thr1043Met)
Germline
Classification Help The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(2) Help Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_015192.4(PLCB1):c.3128C>T (p.Thr1043Met)
Variation ID: 861649 Accession: VCV000861649.7
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 20p12.3 20: 8788465 (GRCh38) [ NCBI UCSC ] 20: 8769112 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 15, 2020 May 1, 2024 Dec 21, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_015192.4:c.3128C>T MANESelect Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_056007.1:p.Thr1043Met missense NM_015192.2:c.3128C>T NM_182734.3:c.3128C>T NP_877398.1:p.Thr1043Met missense NC_000020.11:g.8788465C>T NC_000020.10:g.8769112C>T NG_028168.1:g.660817C>T - Protein change
- T1043M
- Other names
- -
- Canonical SPDI
- NC_000020.11:8788464:C:T
- Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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- Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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- Allele frequency Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00002
Exome Aggregation Consortium (ExAC) 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00003
- Links
- dbSNP: rs754052641
- VarSome
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation | Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases. | Related variants | ||
|---|---|---|---|---|---|---|
| HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. | TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. | Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. | All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. | |||
| PLCB1 | - | - | GRCh38 GRCh37 | 1112 | 1181 | |
Conditions - Germline
| Condition Help The condition for this variant-condition (RCV) record in ClinVar. | Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) | Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. | Last evaluated Help The most recent date that a submitter evaluated this variant for the condition. | Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Developmental and epileptic encephalopathy, 12 | Uncertain significance (1) | Nov 1, 2022 | RCV001068216.5 | |
| Inborn genetic diseases | Uncertain significance (1) | Dec 21, 2022 | RCV002554537.2 |
Submissions - Germline
| Classification Help The submitted germline classification for each SCV record. (Last evaluated) | Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) | Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. | Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. | More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. | |
|---|---|---|---|---|---|
| Uncertain significance (Nov 01, 2022) | (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing | Developmental and epileptic encephalopathy, 12 Affected status: unknown Allele origin: germline | Invitae Accession: SCV001233313.5 | Comment: In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant … (more) In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PLCB1 protein function. ClinVar contains an entry for this variant (Variation ID: 861649). This variant has not been reported in the literature in individuals affected with PLCB1-related conditions. This variant is present in population databases (rs754052641, gnomAD 0.02%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1043 of the PLCB1 protein (p.Thr1043Met). (less) | |
| Uncertain significance (Dec 21, 2022) | (Ambry Variant Classification Scheme 2023) Method: clinical testing | Inborn genetic diseases Affected status: unknown Allele origin: germline | Ambry Genetics Accession: SCV003542945.2 | Comment: The c.3128C>T (p.T1043M) alteration is located in exon 28 (coding exon 28) of the PLCB1 gene. This alteration results from a C to T substitution … (more) The c.3128C>T (p.T1043M) alteration is located in exon 28 (coding exon 28) of the PLCB1 gene. This alteration results from a C to T substitution at nucleotide position 3128, causing the threonine (T) at amino acid position 1043 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less) |
Comment:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PLCB1 protein function. ClinVar contains an entry for this variant (Variation ID: 861649). This variant has not been reported in the literature in individuals affected with PLCB1-related conditions. This variant is present in population databases (rs754052641, gnomAD 0.02%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1043 of the PLCB1 protein (p.Thr1043Met).
Comment:
The c.3128C>T (p.T1043M) alteration is located in exon 28 (coding exon 28) of the PLCB1 gene. This alteration results from a C to T substitution at nucleotide position 3128, causing the threonine (T) at amino acid position 1043 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.
Comment:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PLCB1 protein function. ClinVar contains an entry for this variant (Variation ID: 861649). This variant has not been reported in the literature in individuals affected with PLCB1-related conditions. This variant is present in population databases (rs754052641, gnomAD 0.02%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1043 of the PLCB1 protein (p.Thr1043Met).
Comment:
The c.3128C>T (p.T1043M) alteration is located in exon 28 (coding exon 28) of the PLCB1 gene. This alteration results from a C to T substitution at nucleotide position 3128, causing the threonine (T) at amino acid position 1043 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Citations for germline classification of this variant
Help
There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.
Text-mined citations for rs754052641 ...
Help
These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.
Record last updated May 01, 2024
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