chr3-38613752-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 5P and 4B. PM1PM2PP2BP4_Strong
The NM_000335.5(SCN5A):c.694G>A(p.Val232Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000737 in 1,601,816 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts 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. V232V) has been classified as Likely benign.
Frequency
Consequence
NM_000335.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN5A | NM_000335.5 | c.694G>A | p.Val232Ile | missense_variant | 6/28 | ENST00000423572.7 | |
SCN5A | NM_001099404.2 | c.703+223G>A | intron_variant | ENST00000413689.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN5A | ENST00000423572.7 | c.694G>A | p.Val232Ile | missense_variant | 6/28 | 1 | NM_000335.5 | A1 | |
SCN5A | ENST00000413689.6 | c.703+223G>A | intron_variant | 5 | NM_001099404.2 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000381 AC: 58AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000108 AC: 25AN: 232372Hom.: 0 AF XY: 0.000111 AC XY: 14AN XY: 125568
GnomAD4 exome AF: 0.0000414 AC: 60AN: 1449484Hom.: 1 Cov.: 30 AF XY: 0.0000417 AC XY: 30AN XY: 719984
GnomAD4 genome AF: 0.000381 AC: 58AN: 152332Hom.: 0 Cov.: 33 AF XY: 0.000403 AC XY: 30AN XY: 74482
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 11, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 22, 2021 | This variant is associated with the following publications: (PMID: 23414114, 25637381, 24136861, 24055113, 18599870, 20129283, 29728395, 31535183, 26582918) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 20, 2015 | - - |
Brugada syndrome, lidocaine-induced Uncertain:1
Uncertain significance, no assertion criteria provided | research | CSER _CC_NCGL, University of Washington | Jun 01, 2014 | - - |
Brugada syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Mendelics | Aug 22, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 17, 2021 | 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. - |
Cardiac arrhythmia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jan 15, 2019 | - - |
Brugada syndrome Other:1
not provided, no classification provided | literature only | Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust | - | This variant has been reported as associated with Brugada syndrome in the following publications (PMID:18599870;PMID:20129283). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at