rs747486328
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_006514.4(SCN10A):c.1762G>A(p.Asp588Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,604,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. D588D) has been classified as Likely benign.
Frequency
Consequence
NM_006514.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN10A | NM_006514.4 | c.1762G>A | p.Asp588Asn | missense_variant | 13/28 | ENST00000449082.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN10A | ENST00000449082.3 | c.1762G>A | p.Asp588Asn | missense_variant | 13/28 | 1 | NM_006514.4 | P4 | |
SCN10A | ENST00000655275.1 | c.1789G>A | p.Asp597Asn | missense_variant | 13/28 | ||||
SCN10A | ENST00000643924.1 | c.1762G>A | p.Asp588Asn | missense_variant | 12/27 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000400 AC: 10AN: 249712Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 134944
GnomAD4 exome AF: 0.0000186 AC: 27AN: 1452330Hom.: 0 Cov.: 28 AF XY: 0.0000180 AC XY: 13AN XY: 723018
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74344
ClinVar
Submissions by phenotype
Brugada syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 29, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 588 of the SCN10A protein (p.Asp588Asn). This variant is present in population databases (rs747486328, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SCN10A-related conditions. ClinVar contains an entry for this variant (Variation ID: 407758). 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 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. - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 03, 2023 | 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