rs11711062
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000449082.3(SCN10A):c.4009T>A(p.Ser1337Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00538 in 1,614,206 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
ENST00000449082.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN10A | NM_006514.4 | c.4009T>A | p.Ser1337Thr | missense_variant | 23/28 | ENST00000449082.3 | NP_006505.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN10A | ENST00000449082.3 | c.4009T>A | p.Ser1337Thr | missense_variant | 23/28 | 1 | NM_006514.4 | ENSP00000390600 | P4 | |
SCN10A | ENST00000655275.1 | c.4033T>A | p.Ser1345Thr | missense_variant | 23/28 | ENSP00000499510 | ||||
SCN10A | ENST00000643924.1 | c.4006T>A | p.Ser1336Thr | missense_variant | 22/27 | ENSP00000495595 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00443 AC: 675AN: 152234Hom.: 5 Cov.: 33
GnomAD3 exomes AF: 0.00459 AC: 1154AN: 251418Hom.: 8 AF XY: 0.00461 AC XY: 627AN XY: 135874
GnomAD4 exome AF: 0.00548 AC: 8010AN: 1461854Hom.: 41 Cov.: 32 AF XY: 0.00539 AC XY: 3919AN XY: 727228
GnomAD4 genome AF: 0.00442 AC: 673AN: 152352Hom.: 5 Cov.: 33 AF XY: 0.00427 AC XY: 318AN XY: 74506
ClinVar
Submissions by phenotype
not provided Benign:5
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely 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 | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2024 | SCN10A: BP4, BS1, BS2 - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Apr 01, 2016 | - - |
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 27, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 21, 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. - |
SCN10A-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 17, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Brugada syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 09, 2019 | This alteration is classified as likely 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at