chr3-38580976-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001099404.2(SCN5A):c.3183A>C(p.Glu1061Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000621 in 1,611,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E1061E) has been classified as Likely benign.
Frequency
Consequence
NM_001099404.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN5A | NM_001099404.2 | c.3183A>C | p.Glu1061Asp | missense_variant | 17/28 | ENST00000413689.6 | |
SCN5A | NM_000335.5 | c.3183A>C | p.Glu1061Asp | missense_variant | 17/28 | ENST00000423572.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN5A | ENST00000413689.6 | c.3183A>C | p.Glu1061Asp | missense_variant | 17/28 | 5 | NM_001099404.2 | P4 | |
SCN5A | ENST00000423572.7 | c.3183A>C | p.Glu1061Asp | missense_variant | 17/28 | 1 | NM_000335.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152222Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248548Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134812
GnomAD4 exome AF: 0.00000480 AC: 7AN: 1459112Hom.: 0 Cov.: 65 AF XY: 0.00000552 AC XY: 4AN XY: 725230
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152340Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74490
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 13, 2022 | This variant is present in population databases (rs7430407, gnomAD 0.02%). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 1061 of the SCN5A protein (p.Glu1061Asp). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 639665). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at