rs1555217386
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP2PP3_Moderate
The NM_001330260.2(SCN8A):c.640G>A(p.Gly214Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 9/12 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G214D) has been classified as Uncertain significance.
Frequency
Consequence
NM_001330260.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN8A | NM_001330260.2 | c.640G>A | p.Gly214Ser | missense_variant | 6/27 | ENST00000627620.5 | |
SCN8A | NM_014191.4 | c.706+181G>A | intron_variant | ENST00000354534.11 | |||
SCN8A | NM_001369788.1 | c.640G>A | p.Gly214Ser | missense_variant | 6/26 | ||
SCN8A | NM_001177984.3 | c.706+181G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000627620.5 | c.640G>A | p.Gly214Ser | missense_variant | 6/27 | 5 | NM_001330260.2 | A1 | |
SCN8A | ENST00000354534.11 | c.706+181G>A | intron_variant | 1 | NM_014191.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
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 | May 23, 2023 | 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 sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 530642). This variant has not been reported in the literature in individuals affected with SCN8A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 214 of the SCN8A protein (p.Gly214Ser). The SCN8A gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_001330260.1, and corresponds to NM_014191.3:c.706+181G>A in the primary transcript. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at