12-51794550-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP2PP3_Strong
The NM_014191.4(SCN8A):c.4704G>T(p.Glu1568Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E1568E) has been classified as Likely benign.
Frequency
Consequence
NM_014191.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN8A | NM_001330260.2 | c.4704G>T | p.Glu1568Asp | missense_variant | 26/27 | ENST00000627620.5 | |
SCN8A | NM_014191.4 | c.4704G>T | p.Glu1568Asp | missense_variant | 26/27 | ENST00000354534.11 | |
SCN8A | NM_001177984.3 | c.4581G>T | p.Glu1527Asp | missense_variant | 25/26 | ||
SCN8A | NM_001369788.1 | c.4581G>T | p.Glu1527Asp | missense_variant | 25/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.4704G>T | p.Glu1568Asp | missense_variant | 26/27 | 1 | NM_014191.4 | P4 | |
SCN8A | ENST00000627620.5 | c.4704G>T | p.Glu1568Asp | missense_variant | 26/27 | 5 | NM_001330260.2 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 11, 2017 | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an SCN8A-related disease. This sequence change replaces glutamic acid with aspartic acid at codon 1568 of the SCN8A protein (p.Glu1568Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at