3-38728768-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2
The NM_006514.4(SCN10A):c.2414G>T(p.Gly805Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,614,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G805D) has been classified as Uncertain significance.
Frequency
Consequence
NM_006514.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN10A | NM_006514.4 | c.2414G>T | p.Gly805Val | missense_variant | 16/28 | ENST00000449082.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN10A | ENST00000449082.3 | c.2414G>T | p.Gly805Val | missense_variant | 16/28 | 1 | NM_006514.4 | P4 | |
SCN10A | ENST00000655275.1 | c.2441G>T | p.Gly814Val | missense_variant | 16/28 | ||||
SCN10A | ENST00000643924.1 | c.2414G>T | p.Gly805Val | missense_variant | 15/27 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152128Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000280 AC: 7AN: 249998Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135262
GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461890Hom.: 0 Cov.: 31 AF XY: 0.0000344 AC XY: 25AN XY: 727246
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74310
ClinVar
Submissions by phenotype
Brugada syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 22, 2022 | ClinVar contains an entry for this variant (Variation ID: 574720). 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 expected to disrupt SCN10A protein function. 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. This missense change has been observed in individual(s) with clinical features of SCN10A-related disease (PMID: 30177317). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 805 of the SCN10A protein (p.Gly805Val). This variant is present in population databases (rs779733116, gnomAD 0.006%). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 09, 2022 | Identified in a patient with sudden cardiac arrest and an abnormal ECG (Di Stolfo et al., 2018); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34426522, 30177317, 27535533, 26582918) - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 06, 2020 | The p.G805V variant (also known as c.2414G>T), located in coding exon 15 of the SCN10A gene, results from a G to T substitution at nucleotide position 2414. The glycine at codon 805 is replaced by valine, an amino acid with dissimilar properties. This alteration has been reported in a single case of sudden cardiac death due to early repolarization syndrome; however an environmental modifier may have played a role in the phenotypic expression of this variant (Di Stolfo G et al. J Electrocardiol Jun;51:809-813). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at