ClinVar Genomic variation as it relates to human health
NM_018896.5(CACNA1G):c.1888A>T (p.Ser630Cys)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_018896.5(CACNA1G):c.1888A>T (p.Ser630Cys)
Variation ID: 977088 Accession: VCV000977088.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.33 17: 50576290 (GRCh38) [ NCBI UCSC ] 17: 48653651 (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 Aug 22, 2020 Feb 20, 2024 Dec 31, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_018896.5:c.1888A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_061496.2:p.Ser630Cys missense NM_001256324.2:c.1888A>T NP_001243253.1:p.Ser630Cys missense NM_001256325.2:c.1888A>T NP_001243254.1:p.Ser630Cys missense NM_001256326.2:c.1888A>T NP_001243255.1:p.Ser630Cys missense NM_001256327.2:c.1888A>T NP_001243256.1:p.Ser630Cys missense NM_001256328.2:c.1888A>T NP_001243257.1:p.Ser630Cys missense NM_001256329.2:c.1888A>T NP_001243258.1:p.Ser630Cys missense NM_001256330.2:c.1888A>T NP_001243259.1:p.Ser630Cys missense NM_001256331.2:c.1888A>T NP_001243260.1:p.Ser630Cys missense NM_001256332.2:c.1888A>T NP_001243261.1:p.Ser630Cys missense NM_001256333.2:c.1888A>T NP_001243262.1:p.Ser630Cys missense NM_001256334.2:c.1888A>T NP_001243263.1:p.Ser630Cys missense NM_001256359.2:c.1888A>T NP_001243288.1:p.Ser630Cys missense NM_001256360.2:c.1888A>T NP_001243289.1:p.Ser630Cys missense NM_001256361.2:c.1888A>T NP_001243290.1:p.Ser630Cys missense NM_198376.3:c.1888A>T NP_938190.1:p.Ser630Cys missense NM_198377.3:c.1888A>T NP_938191.2:p.Ser630Cys missense NM_198378.3:c.1888A>T NP_938192.1:p.Ser630Cys missense NM_198379.3:c.1888A>T NP_938193.1:p.Ser630Cys missense NM_198380.3:c.1888A>T NP_938194.1:p.Ser630Cys missense NM_198382.3:c.1888A>T NP_938196.1:p.Ser630Cys missense NM_198383.3:c.1888A>T NP_938197.1:p.Ser630Cys missense NM_198384.3:c.1888A>T NP_938198.1:p.Ser630Cys missense NM_198385.3:c.1888A>T NP_938199.1:p.Ser630Cys missense NM_198386.3:c.1888A>T NP_938200.1:p.Ser630Cys missense NM_198387.3:c.1888A>T NP_938201.1:p.Ser630Cys missense NM_198388.3:c.1888A>T NP_938202.1:p.Ser630Cys missense NM_198396.3:c.1888A>T NP_938406.1:p.Ser630Cys missense NR_046054.2:n.2633A>T non-coding transcript variant NR_046055.2:n.2633A>T non-coding transcript variant NR_046056.2:n.2633A>T non-coding transcript variant NR_046057.2:n.2633A>T non-coding transcript variant NR_046058.2:n.2633A>T non-coding transcript variant NC_000017.11:g.50576290A>T NC_000017.10:g.48653651A>T NG_032024.1:g.20223A>T - Protein change
- S630C
- Other names
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- Canonical SPDI
- NC_000017.11:50576289:A:T
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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
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00004
Exome Aggregation Consortium (ExAC) 0.00006
The Genome Aggregation Database (gnomAD) 0.00006
Trans-Omics for Precision Medicine (TOPMed) 0.00006
- Links
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 | ||
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HI score
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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. |
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CACNA1G | - | - |
GRCh38 GRCh37 |
952 | 988 |
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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (1) |
criteria provided, single submitter
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Jun 3, 2020 | RCV001254615.1 | |
Uncertain significance (1) |
criteria provided, single submitter
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Dec 31, 2022 | RCV003718389.1 |
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
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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. |
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Uncertain significance
(Jun 03, 2020)
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criteria provided, single submitter
Method: clinical testing
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Spinocerebellar ataxia type 42
Affected status: unknown
Allele origin:
germline
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Johns Hopkins Genomics, Johns Hopkins University
Accession: SCV001430632.1
First in ClinVar: Aug 22, 2020 Last updated: Aug 22, 2020 |
Comment:
This CACNA1G variant (rs779077930) is rare (<0.1%) in a large population dataset (gnomAD: 7/192408 total alleles; 0.004%; no homozygotes) and has not been reported previously … (more)
This CACNA1G variant (rs779077930) is rare (<0.1%) in a large population dataset (gnomAD: 7/192408 total alleles; 0.004%; no homozygotes) and has not been reported previously in the literature to our knowledge. Two bioinformatic tools queried predict that p.Ser630Cys would be damaging, and the serine residue at this position is strongly conserved across the vertebrate species assessed. This variant is not predicted to affect normal exon 8 splicing, although this has not been confirmed experimentally to our knowledge. We consider the clinical significance of c.1888A>T to be uncertain at this time. (less)
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Uncertain significance
(Dec 31, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV004510039.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CACNA1G protein function. ClinVar contains an entry for this variant (Variation ID: 977088). This variant has not been reported in the literature in individuals affected with CACNA1G-related conditions. This variant is present in population databases (rs779077930, gnomAD 0.009%). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 630 of the CACNA1G protein (p.Ser630Cys). (less)
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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A mutation in the low voltage-gated calcium channel CACNA1G alters the physiological properties of the channel, causing spinocerebellar ataxia. | Morino H | Molecular brain | 2015 | PMID: 26715324 |
A Recurrent Mutation in CACNA1G Alters Cav3.1 T-Type Calcium-Channel Conduction and Causes Autosomal-Dominant Cerebellar Ataxia. | Coutelier M | American journal of human genetics | 2015 | PMID: 26456284 |
Text-mined citations for rs779077930 ...
HelpRecord last updated Feb 28, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.