rs202040659
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_006514.4(SCN10A):c.4552G>A(p.Val1518Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000514 in 1,614,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. V1518V) 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 -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN10A | NM_006514.4 | c.4552G>A | p.Val1518Ile | missense_variant | 27/28 | ENST00000449082.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN10A | ENST00000449082.3 | c.4552G>A | p.Val1518Ile | missense_variant | 27/28 | 1 | NM_006514.4 | P4 | |
SCN10A | ENST00000655275.1 | c.4576G>A | p.Val1526Ile | missense_variant | 27/28 | ||||
SCN10A | ENST00000643924.1 | c.4549G>A | p.Val1517Ile | missense_variant | 26/27 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000177 AC: 27AN: 152168Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000717 AC: 18AN: 251220Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135754
GnomAD4 exome AF: 0.0000383 AC: 56AN: 1461824Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28AN XY: 727212
GnomAD4 genome AF: 0.000177 AC: 27AN: 152286Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74460
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 24, 2020 | Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 532075; Landrum et al., 2016); Functional studies suggest this variant affects sodium channel function (Gando et al., 2019); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31195250) - |
Brugada syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 19, 2019 | 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