rs184442491
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 5P and 5B. PM2PM5PP2BP4_StrongBP6
The ENST00000423572.7(SCN5A):c.1714G>T(p.Ala572Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. A572F) has been classified as Likely benign.
Frequency
Consequence
ENST00000423572.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN5A | NM_001099404.2 | c.1714G>T | p.Ala572Ser | missense_variant | 12/28 | ENST00000413689.6 | NP_001092874.1 | |
SCN5A | NM_000335.5 | c.1714G>T | p.Ala572Ser | missense_variant | 12/28 | ENST00000423572.7 | NP_000326.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN5A | ENST00000413689.6 | c.1714G>T | p.Ala572Ser | missense_variant | 12/28 | 5 | NM_001099404.2 | ENSP00000410257 | P4 | |
SCN5A | ENST00000423572.7 | c.1714G>T | p.Ala572Ser | missense_variant | 12/28 | 1 | NM_000335.5 | ENSP00000398266 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000749 AC: 114AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000209 AC: 52AN: 248984Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135066
GnomAD4 exome AF: 0.0000807 AC: 118AN: 1461650Hom.: 0 Cov.: 31 AF XY: 0.0000715 AC XY: 52AN XY: 727118
GnomAD4 genome AF: 0.000748 AC: 114AN: 152324Hom.: 0 Cov.: 32 AF XY: 0.000779 AC XY: 58AN XY: 74476
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 31, 2016 | 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 in 1 paper; 2 additional papers describe presence in control dbs; ExAC: 0.2% (19/9774) African; ClinVar: 1 VUS - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 28, 2024 | - - |
Brugada syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Long QT syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | research | CSER _CC_NCGL, University of Washington | Jun 01, 2014 | Low GERP score may suggest that this variant may belong in a lower pathogenicity class - |
Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Jan 25, 2023 | - - |
Congenital long QT 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 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