3-38697357-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006514.4(SCN10A):c.5863G>A(p.Gly1955Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN10A | ENST00000449082.3 | c.5863G>A | p.Gly1955Arg | missense_variant | Exon 28 of 28 | 1 | NM_006514.4 | ENSP00000390600.2 | ||
SCN10A | ENST00000643924.1 | c.5860G>A | p.Gly1954Arg | missense_variant | Exon 27 of 27 | ENSP00000495595.1 | ||||
SCN10A | ENST00000655275.1 | c.5887G>A | p.Gly1963Arg | missense_variant | Exon 28 of 28 | ENSP00000499510.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Brugada syndrome Uncertain:1
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. 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. ClinVar contains an entry for this variant (Variation ID: 809452). This variant has not been reported in the literature in individuals affected with SCN10A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1955 of the SCN10A protein (p.Gly1955Arg). -
Cardiovascular phenotype Uncertain:1
The p.G1955R variant (also known as c.5863G>A), located in coding exon 27 of the SCN10A gene, results from a G to A substitution at nucleotide position 5863. The glycine at codon 1955 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at