12-51688790-T-G
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP2PP3_ModeratePP5
The NM_014191.4(SCN8A):c.647T>G(p.Val216Gly) 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. 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. V216D) has been classified as Uncertain significance.
Frequency
Consequence
NM_014191.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN8A | NM_014191.4 | c.647T>G | p.Val216Gly | missense_variant | 6/27 | ENST00000354534.11 | |
SCN8A | NM_001330260.2 | c.615-215T>G | intron_variant | ENST00000627620.5 | |||
SCN8A | NM_001177984.3 | c.647T>G | p.Val216Gly | missense_variant | 6/26 | ||
SCN8A | NM_001369788.1 | c.615-215T>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.647T>G | p.Val216Gly | missense_variant | 6/27 | 1 | NM_014191.4 | P4 | |
SCN8A | ENST00000627620.5 | c.615-215T>G | intron_variant | 5 | NM_001330260.2 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 13 Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Baylor Genetics | Oct 03, 2014 | Our laboratory reported dual molecular diagnoses in SCN8A (NM_014191.3, c.647T>G) and MAN2B1 (NM_000528.3, c.2782G>C and c.1383C>G in trans) in one individual with reported features that include delayed motor milestones, delayed speech, intellectual disability, hypotonia, seizure disorder (refractory epilepsy), abnormal movements (dyskinesia), minor dysmorphic features (flat nasal bridge, prominent eyes, full lips), microcephaly, dysphagia, and cortical visual impairment. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at