rs7617919
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_006514.4(SCN10A):c.1476C>T(p.Leu492=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 1,588,222 control chromosomes in the GnomAD database, including 47,347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.21 ( 3705 hom., cov: 32)
Exomes 𝑓: 0.24 ( 43642 hom. )
Consequence
SCN10A
NM_006514.4 synonymous
NM_006514.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.20
Genes affected
SCN10A (HGNC:10582): (sodium voltage-gated channel alpha subunit 10) The protein encoded by this gene is a tetrodotoxin-resistant voltage-gated sodium channel alpha subunit. The properties of the channel formed by the encoded transmembrane protein can be altered by interaction with different beta subunits. This protein may be involved in the onset of pain associated with peripheral neuropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 3-38752498-G-A is Benign according to our data. Variant chr3-38752498-G-A is described in ClinVar as [Benign]. Clinvar id is 259992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38752498-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-1.2 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN10A | NM_006514.4 | c.1476C>T | p.Leu492= | synonymous_variant | 12/28 | ENST00000449082.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN10A | ENST00000449082.3 | c.1476C>T | p.Leu492= | synonymous_variant | 12/28 | 1 | NM_006514.4 | P4 | |
SCN10A | ENST00000655275.1 | c.1503C>T | p.Leu501= | synonymous_variant | 12/28 | ||||
SCN10A | ENST00000643924.1 | c.1476C>T | p.Leu492= | synonymous_variant | 11/27 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.206 AC: 31307AN: 152038Hom.: 3705 Cov.: 32
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GnomAD3 exomes AF: 0.233 AC: 53412AN: 229124Hom.: 6923 AF XY: 0.239 AC XY: 29589AN XY: 123944
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GnomAD4 exome AF: 0.241 AC: 346768AN: 1436066Hom.: 43642 Cov.: 33 AF XY: 0.242 AC XY: 172275AN XY: 711868
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GnomAD4 genome ? AF: 0.206 AC: 31310AN: 152156Hom.: 3705 Cov.: 32 AF XY: 0.207 AC XY: 15411AN XY: 74368
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 09, 2023 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute | May 18, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 23, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Episodic pain syndrome, familial, 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Brugada syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 21, 2018 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at