NM_001330260.2:c.3710A>G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4BP6BS2
The NM_001330260.2(SCN8A):āc.3710A>Gā(p.Lys1237Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000452 in 1,613,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001330260.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN8A | NM_001330260.2 | c.3710A>G | p.Lys1237Arg | missense_variant | Exon 20 of 27 | ENST00000627620.5 | NP_001317189.1 | |
SCN8A | NM_014191.4 | c.3710A>G | p.Lys1237Arg | missense_variant | Exon 20 of 27 | ENST00000354534.11 | NP_055006.1 | |
SCN8A | NM_001177984.3 | c.3710A>G | p.Lys1237Arg | missense_variant | Exon 20 of 26 | NP_001171455.1 | ||
SCN8A | NM_001369788.1 | c.3710A>G | p.Lys1237Arg | missense_variant | Exon 20 of 26 | NP_001356717.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.3710A>G | p.Lys1237Arg | missense_variant | Exon 20 of 27 | 1 | NM_014191.4 | ENSP00000346534.4 | ||
SCN8A | ENST00000627620.5 | c.3710A>G | p.Lys1237Arg | missense_variant | Exon 20 of 27 | 5 | NM_001330260.2 | ENSP00000487583.2 | ||
SCN8A | ENST00000599343.5 | c.3743A>G | p.Lys1248Arg | missense_variant | Exon 19 of 26 | 5 | ENSP00000476447.3 | |||
SCN8A | ENST00000355133.7 | c.3710A>G | p.Lys1237Arg | missense_variant | Exon 19 of 25 | 1 | ENSP00000347255.4 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152196Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250462Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135732
GnomAD4 exome AF: 0.0000431 AC: 63AN: 1461770Hom.: 0 Cov.: 30 AF XY: 0.0000413 AC XY: 30AN XY: 727190
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74352
ClinVar
Submissions by phenotype
SCN8A-related disorder Uncertain:1
The SCN8A c.3710A>G variant is predicted to result in the amino acid substitution p.Lys1237Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0023% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
not provided Uncertain:1
A variant of uncertain significance has been identified in the SCN8A gene. The K1237R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The K1237R variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution alters a position conserved in mammals that is predicted to be within the transmembrane segment S2 of the third homologous domain. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the K1237R variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. -
Early infantile epileptic encephalopathy with suppression bursts Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at