rs746302474
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_014191.4(SCN8A):āc.3230A>Gā(p.Tyr1077Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y1077H) has been classified as Uncertain significance.
Frequency
Consequence
NM_014191.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN8A | NM_001330260.2 | c.3230A>G | p.Tyr1077Cys | missense_variant | 17/27 | ENST00000627620.5 | |
SCN8A | NM_014191.4 | c.3230A>G | p.Tyr1077Cys | missense_variant | 17/27 | ENST00000354534.11 | |
SCN8A | NM_001177984.3 | c.3230A>G | p.Tyr1077Cys | missense_variant | 17/26 | ||
SCN8A | NM_001369788.1 | c.3230A>G | p.Tyr1077Cys | missense_variant | 17/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.3230A>G | p.Tyr1077Cys | missense_variant | 17/27 | 1 | NM_014191.4 | P4 | |
SCN8A | ENST00000627620.5 | c.3230A>G | p.Tyr1077Cys | missense_variant | 17/27 | 5 | NM_001330260.2 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152246Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249576Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135128
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461590Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727060
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74390
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 21, 2018 | This sequence change replaces tyrosine with cysteine at codon 1077 of the SCN8A protein (p.Tyr1077Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs746302474, ExAC 0.003%). This variant has not been reported in the literature in individuals with SCN8A-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at