rs187153231
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_014191.4(SCN8A):āc.2098A>Gā(p.Ile700Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I700L) has been classified as Likely benign.
Frequency
Consequence
NM_014191.4 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN8A | NM_001330260.2 | c.2098A>G | p.Ile700Val | missense_variant | 13/27 | ENST00000627620.5 | |
SCN8A | NM_014191.4 | c.2098A>G | p.Ile700Val | missense_variant | 13/27 | ENST00000354534.11 | |
SCN8A | NM_001177984.3 | c.2098A>G | p.Ile700Val | missense_variant | 13/26 | ||
SCN8A | NM_001369788.1 | c.2098A>G | p.Ile700Val | missense_variant | 13/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.2098A>G | p.Ile700Val | missense_variant | 13/27 | 1 | NM_014191.4 | P4 | |
SCN8A | ENST00000627620.5 | c.2098A>G | p.Ile700Val | missense_variant | 13/27 | 5 | NM_001330260.2 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1459256Hom.: 0 Cov.: 32 AF XY: 0.00000551 AC XY: 4AN XY: 725776
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 | Nov 24, 2022 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SCN8A protein function. ClinVar contains an entry for this variant (Variation ID: 859199). 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 isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 700 of the SCN8A protein (p.Ile700Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at