rs376150162
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001099404.2(SCN5A):c.4935G>A(p.Thr1645=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000613 in 1,614,138 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T1645T) has been classified as Likely benign.
Frequency
Consequence
NM_001099404.2 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN5A | NM_001099404.2 | c.4935G>A | p.Thr1645= | synonymous_variant | 28/28 | ENST00000413689.6 | |
SCN5A | NM_000335.5 | c.4932G>A | p.Thr1644= | synonymous_variant | 28/28 | ENST00000423572.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN5A | ENST00000413689.6 | c.4935G>A | p.Thr1645= | synonymous_variant | 28/28 | 5 | NM_001099404.2 | P4 | |
SCN5A | ENST00000423572.7 | c.4932G>A | p.Thr1644= | synonymous_variant | 28/28 | 1 | NM_000335.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000276 AC: 42AN: 152134Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251480Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135914
GnomAD4 exome AF: 0.0000390 AC: 57AN: 1461886Hom.: 0 Cov.: 35 AF XY: 0.0000426 AC XY: 31AN XY: 727240
GnomAD4 genome ? AF: 0.000276 AC: 42AN: 152252Hom.: 0 Cov.: 31 AF XY: 0.000255 AC XY: 19AN XY: 74440
ClinVar
Submissions by phenotype
Cardiac arrhythmia Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 08, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Jan 11, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 28, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
SCN5A-related condition Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 21, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2016 | 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