rs6795970
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_006514.4(SCN10A):āc.3218T>Cā(p.Val1073Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 1,594,466 control chromosomes in the GnomAD database, including 318,682 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1073I) has been classified as Uncertain significance.
Frequency
Consequence
NM_006514.4 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 | UniProt |
---|---|---|---|---|---|---|---|
SCN10A | NM_006514.4 | c.3218T>C | p.Val1073Ala | missense_variant | 18/28 | ENST00000449082.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN10A | ENST00000449082.3 | c.3218T>C | p.Val1073Ala | missense_variant | 18/28 | 1 | NM_006514.4 | P4 | |
SCN10A | ENST00000655275.1 | c.3242T>C | p.Val1081Ala | missense_variant | 18/28 | ||||
SCN10A | ENST00000643924.1 | c.3215T>C | p.Val1072Ala | missense_variant | 17/27 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.700 AC: 106402AN: 151966Hom.: 38689 Cov.: 32
GnomAD3 exomes AF: 0.652 AC: 161934AN: 248186Hom.: 54207 AF XY: 0.644 AC XY: 86354AN XY: 134142
GnomAD4 exome AF: 0.619 AC: 893149AN: 1442382Hom.: 279919 Cov.: 45 AF XY: 0.618 AC XY: 442210AN XY: 715412
GnomAD4 genome ? AF: 0.701 AC: 106542AN: 152084Hom.: 38763 Cov.: 32 AF XY: 0.699 AC XY: 51984AN XY: 74352
ClinVar
Submissions by phenotype
not specified Benign:6
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 04, 2023 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
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 | GeneDx | Sep 22, 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. - |
Benign, criteria provided, single submitter | clinical testing | Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute | Jun 10, 2016 | - - |
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 03, 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at