rs148537653
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2
The NM_006514.4(SCN10A):c.5540G>A(p.Arg1847Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,614,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006514.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN10A | ENST00000449082.3 | c.5540G>A | p.Arg1847Gln | missense_variant | Exon 28 of 28 | 1 | NM_006514.4 | ENSP00000390600.2 | ||
SCN10A | ENST00000643924.1 | c.5537G>A | p.Arg1846Gln | missense_variant | Exon 27 of 27 | ENSP00000495595.1 | ||||
SCN10A | ENST00000655275.1 | c.5564G>A | p.Arg1855Gln | missense_variant | Exon 28 of 28 | ENSP00000499510.1 |
Frequencies
GnomAD3 genomes AF: 0.0000921 AC: 14AN: 152084Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000916 AC: 23AN: 251148Hom.: 0 AF XY: 0.0000884 AC XY: 12AN XY: 135716
GnomAD4 exome AF: 0.000111 AC: 163AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.0000839 AC XY: 61AN XY: 727246
GnomAD4 genome AF: 0.0000920 AC: 14AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74412
ClinVar
Submissions by phenotype
not provided Uncertain:1
Identified in a patient with corneal neuralgia in published literature (Yuan et al., 2020); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32766464) -
Brugada syndrome Benign:1
- -
Cardiovascular phenotype Benign:1
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