rs202151337
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP2PP3_ModeratePP5_Moderate
The NM_001330260.2(SCN8A):c.5302A>G(p.Asn1768Asp) 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 Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. N1768N) has been classified as Likely benign.
Frequency
Consequence
NM_001330260.2 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN8A | NM_001330260.2 | c.5302A>G | p.Asn1768Asp | missense_variant | Exon 27 of 27 | ENST00000627620.5 | NP_001317189.1 | |
SCN8A | NM_014191.4 | c.5302A>G | p.Asn1768Asp | missense_variant | Exon 27 of 27 | ENST00000354534.11 | NP_055006.1 | |
SCN8A | NM_001177984.3 | c.5179A>G | p.Asn1727Asp | missense_variant | Exon 26 of 26 | NP_001171455.1 | ||
SCN8A | NM_001369788.1 | c.5179A>G | p.Asn1727Asp | missense_variant | Exon 26 of 26 | NP_001356717.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.5302A>G | p.Asn1768Asp | missense_variant | Exon 27 of 27 | 1 | NM_014191.4 | ENSP00000346534.4 | ||
SCN8A | ENST00000627620.5 | c.5302A>G | p.Asn1768Asp | missense_variant | Exon 27 of 27 | 5 | NM_001330260.2 | ENSP00000487583.2 | ||
SCN8A | ENST00000599343.5 | c.5335A>G | p.Asn1779Asp | missense_variant | Exon 26 of 26 | 5 | ENSP00000476447.3 | |||
SCN8A | ENST00000355133.7 | c.5179A>G | p.Asn1727Asp | missense_variant | Exon 25 of 25 | 1 | ENSP00000347255.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 13 Pathogenic:1Other:1
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Early infantile epileptic encephalopathy with suppression bursts Pathogenic:1
This sequence change replaces asparagine with aspartic acid at codon 1768 of the SCN8A protein (p.Asn1768Asp). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with epileptic encephalopathy (PMID: 22365152, 29186148). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 30123). This variant has been reported to affect SCN8A protein function (PMID: 22365152, 25227913, 28676574). For these reasons, this variant has been classified as Pathogenic. -
Complex neurodevelopmental disorder Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at