rs137854601
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The ENST00000423572.7(SCN5A):c.5347G>T(p.Glu1783Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SCN5A
ENST00000423572.7 stop_gained
ENST00000423572.7 stop_gained
Scores
5
1
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.14
Genes affected
SCN5A (HGNC:10593): (sodium voltage-gated channel alpha subunit 5) The protein encoded by this gene is an integral membrane protein and tetrodotoxin-resistant voltage-gated sodium channel subunit. This protein is found primarily in cardiac muscle and is responsible for the initial upstroke of the action potential in an electrocardiogram. Defects in this gene have been associated with long QT syndrome type 3 (LQT3), atrial fibrillation, cardiomyopathy, and Brugada syndrome 1, all autosomal dominant cardiac diseases. Alternative splicing results in several transcript variants encoding different isoforms. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 52 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN5A | NM_001099404.2 | c.5350G>T | p.Glu1784Ter | stop_gained | 28/28 | ENST00000413689.6 | NP_001092874.1 | |
SCN5A | NM_000335.5 | c.5347G>T | p.Glu1783Ter | stop_gained | 28/28 | ENST00000423572.7 | NP_000326.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN5A | ENST00000413689.6 | c.5350G>T | p.Glu1784Ter | stop_gained | 28/28 | 5 | NM_001099404.2 | ENSP00000410257 | P4 | |
SCN5A | ENST00000423572.7 | c.5347G>T | p.Glu1783Ter | stop_gained | 28/28 | 1 | NM_000335.5 | ENSP00000398266 | A1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251008Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135840
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461894Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 727248
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GnomAD4 genome Cov.: 31
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31
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at