ClinVar Genomic variation as it relates to human health
NM_003098.3(SNTA1):c.566C>T (p.Ser189Leu)
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.
Uncertain significance(3); Likely benign(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_003098.3(SNTA1):c.566C>T (p.Ser189Leu)
Variation ID: 263623 Accession: VCV000263623.29
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 20q11.21 20: 33417854 (GRCh38) [ NCBI UCSC ] 20: 32005660 (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 Oct 3, 2016 Feb 14, 2024 Dec 24, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003098.3:c.566C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003089.1:p.Ser189Leu missense NC_000020.11:g.33417854G>A NC_000020.10:g.32005660G>A NG_011622.1:g.31039C>T LRG_332:g.31039C>T LRG_332t1:c.566C>T LRG_332p1:p.Ser189Leu - Protein change
- S189L
- Other names
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- Canonical SPDI
- NC_000020.11:33417853:G:A
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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) 0.00020
The Genome Aggregation Database (gnomAD), exomes 0.00020
Trans-Omics for Precision Medicine (TOPMed) 0.00020
Exome Aggregation Consortium (ExAC) 0.00021
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00023
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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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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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SNTA1 | - | - |
GRCh38 GRCh37 |
400 | 501 |
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
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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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Likely benign (1) |
criteria provided, single submitter
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Mar 28, 2022 | RCV000251711.2 | |
Uncertain significance (1) |
criteria provided, single submitter
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Mar 30, 2018 | RCV000624991.7 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Jan 4, 2021 | RCV000587989.12 | |
Uncertain significance (1) |
criteria provided, single submitter
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Dec 24, 2023 | RCV001213908.4 |
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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Likely benign
(Apr 26, 2016)
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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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000698166.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The c.566C>T in SNTA1 gene is a missense change that alters a highly conserved nucleotide and 3/4 in silico tools predict deleterious outcome. … (more)
Variant summary: The c.566C>T in SNTA1 gene is a missense change that alters a highly conserved nucleotide and 3/4 in silico tools predict deleterious outcome. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.02%, predominantly in individuals of European descent (0.03%). These frequencies exceed the maximal expected allele frequency for a pathogenic variant in SNTA1 gene (0.001%). The variant of interest has not, to our knowledge, been reported in affected individuals in published reports or cited by a reputable database/diagnostic center. Taking together, the variant was classified as Likely Benign. (less)
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Uncertain significance
(Mar 30, 2018)
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criteria provided, single submitter
Method: clinical testing
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Long QT syndrome 12
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001303915.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
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Uncertain significance
(Jan 04, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001771674.1
First in ClinVar: Aug 07, 2021 Last updated: Aug 07, 2021 |
Comment:
Variant has been reported in the literature in patients with lone atrial fibrillation, unspecified arrhythmia, ARVC, and/or sudden cardiac death, most of whom also harbored … (more)
Variant has been reported in the literature in patients with lone atrial fibrillation, unspecified arrhythmia, ARVC, and/or sudden cardiac death, most of whom also harbored additional cardiac variants thought to contribute to disease (Husser et al., 2017; Proost et al., 2017, van Lint et al., 2019); Reported in ClinVar but additional evidence is not available (ClinVar Variant ID #263623; Landrum et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30847666, 28837624, 28341588) (less)
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Likely benign
(Mar 28, 2022)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000318682.6
First in ClinVar: Oct 03, 2016 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, … (more)
This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Number of individuals with the variant: 1
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Uncertain significance
(Dec 24, 2023)
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criteria provided, single submitter
Method: clinical testing
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Long QT syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001385564.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 189 of the SNTA1 protein (p.Ser189Leu). … (more)
This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 189 of the SNTA1 protein (p.Ser189Leu). This variant is present in population databases (rs144860423, gnomAD 0.04%). This missense change has been observed in individual(s) with atrial fibrillation, arrhythmogenic right ventricular cardiomyopathy, sudden infant death syndrome, and sudden cardiac arrest (PMID: 28074886, 28837624, 30847666, 30975432). ClinVar contains an entry for this variant (Variation ID: 263623). 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 SNTA1 protein function with a negative predictive value of 80%. 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. (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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Modifier genes in SCN1A-related epilepsy syndromes. | de Lange IM | Molecular genetics & genomic medicine | 2020 | PMID: 32032478 |
Usefulness of Genetic Testing in Sudden Cardiac Arrest Survivors With or Without Previous Clinical Evidence of Heart Disease. | Asatryan B | The American journal of cardiology | 2019 | PMID: 30975432 |
Large next-generation sequencing gene panels in genetic heart disease: yield of pathogenic variants and variants of unknown significance. | van Lint FHM | Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation | 2019 | PMID: 30847666 |
Identification of putative pathogenic single nucleotide variants (SNVs) in genes associated with heart disease in 290 cases of stillbirth. | Sahlin E | PloS one | 2019 | PMID: 30615648 |
Rare variants in genes encoding the cardiac sodium channel and associated compounds and their impact on outcome of catheter ablation of atrial fibrillation. | Husser D | PloS one | 2017 | PMID: 28837624 |
Targeted Next-Generation Sequencing of 51 Genes Involved in Primary Electrical Disease. | Proost D | The Journal of molecular diagnostics : JMD | 2017 | PMID: 28341588 |
Post-mortem whole-exome analysis in a large sudden infant death syndrome cohort with a focus on cardiovascular and metabolic genetic diseases. | Neubauer J | European journal of human genetics : EJHG | 2017 | PMID: 28074886 |
Text-mined citations for rs144860423 ...
HelpRecord last updated Feb 20, 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.