rs36210423
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 5P and 9B. PM2PM5PP2BP4_StrongBP6BS1
The NM_000335.5(SCN5A):c.1715C>T(p.Ala572Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,613,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A572D) has been classified as Pathogenic.
Frequency
Consequence
NM_000335.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN5A | NM_001099404.2 | c.1715C>T | p.Ala572Val | missense_variant | Exon 12 of 28 | ENST00000413689.6 | NP_001092874.1 | |
SCN5A | NM_000335.5 | c.1715C>T | p.Ala572Val | missense_variant | Exon 12 of 28 | ENST00000423572.7 | NP_000326.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN5A | ENST00000413689.6 | c.1715C>T | p.Ala572Val | missense_variant | Exon 12 of 28 | 5 | NM_001099404.2 | ENSP00000410257.1 | ||
SCN5A | ENST00000423572.7 | c.1715C>T | p.Ala572Val | missense_variant | Exon 12 of 28 | 1 | NM_000335.5 | ENSP00000398266.2 |
Frequencies
GnomAD3 genomes AF: 0.000742 AC: 113AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000209 AC: 52AN: 248994Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135080
GnomAD4 exome AF: 0.0000842 AC: 123AN: 1461636Hom.: 0 Cov.: 31 AF XY: 0.0000770 AC XY: 56AN XY: 727118
GnomAD4 genome AF: 0.000742 AC: 113AN: 152324Hom.: 0 Cov.: 32 AF XY: 0.000779 AC XY: 58AN XY: 74460
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported by 1 paper; ExAC: 0.2% (19/9772) African -
Brugada syndrome 1 Uncertain:1
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Cardiomyopathy Benign:1
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not provided Benign:1
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Congenital long QT syndrome Other:1
This variant has been reported as associated with Long QT syndrome in the following publications (PMID:19716085). 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