chr12-51806756-T-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP2PP3_ModeratePP5
The NM_014191.4(SCN8A):c.5270T>A(p.Val1757Asp) 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. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1757I) has been classified as Uncertain significance.
Frequency
Consequence
NM_014191.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN8A | NM_001330260.2 | c.5270T>A | p.Val1757Asp | missense_variant | 27/27 | ENST00000627620.5 | |
SCN8A | NM_014191.4 | c.5270T>A | p.Val1757Asp | missense_variant | 27/27 | ENST00000354534.11 | |
SCN8A | NM_001177984.3 | c.5147T>A | p.Val1716Asp | missense_variant | 26/26 | ||
SCN8A | NM_001369788.1 | c.5147T>A | p.Val1716Asp | missense_variant | 26/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.5270T>A | p.Val1757Asp | missense_variant | 27/27 | 1 | NM_014191.4 | P4 | |
SCN8A | ENST00000627620.5 | c.5270T>A | p.Val1757Asp | missense_variant | 27/27 | 5 | NM_001330260.2 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
SCN8A-related disorder Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals | May 04, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at