3-38587413-C-T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP2PP3_Strong
The NM_001099404.2(SCN5A):c.2423G>A(p.Arg808His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 14/22 in silico tools predict a damaging 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. R808C) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001099404.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN5A | NM_001099404.2 | c.2423G>A | p.Arg808His | missense_variant | 15/28 | ENST00000413689.6 | |
SCN5A | NM_000335.5 | c.2423G>A | p.Arg808His | missense_variant | 15/28 | ENST00000423572.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN5A | ENST00000413689.6 | c.2423G>A | p.Arg808His | missense_variant | 15/28 | 5 | NM_001099404.2 | P4 | |
SCN5A | ENST00000423572.7 | c.2423G>A | p.Arg808His | missense_variant | 15/28 | 1 | NM_000335.5 | A1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000404 AC: 1AN: 247724Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134272
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1460462Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726324
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Cardiac arrhythmia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jul 27, 2021 | This missense variant replaces arginine with histidine at codon 808 of the SCN5A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/247724 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Apr 27, 2023 | - - |
Long QT syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at