rs764115258
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The NM_014191.4(SCN8A):āc.5479A>Gā(p.Ile1827Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,824 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I1827T) 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_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN8A | NM_001330260.2 | c.5479A>G | p.Ile1827Val | missense_variant | 27/27 | ENST00000627620.5 | |
SCN8A | NM_014191.4 | c.5479A>G | p.Ile1827Val | missense_variant | 27/27 | ENST00000354534.11 | |
SCN8A | NM_001177984.3 | c.5356A>G | p.Ile1786Val | missense_variant | 26/26 | ||
SCN8A | NM_001369788.1 | c.5356A>G | p.Ile1786Val | missense_variant | 26/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.5479A>G | p.Ile1827Val | missense_variant | 27/27 | 1 | NM_014191.4 | P4 | |
SCN8A | ENST00000627620.5 | c.5479A>G | p.Ile1827Val | missense_variant | 27/27 | 5 | NM_001330260.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249586Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135370
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461692Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727126
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74320
ClinVar
Submissions by phenotype
Cognitive impairment with or without cerebellar ataxia;C3281191:Developmental and epileptic encephalopathy, 13;C4310728:Seizures, benign familial infantile, 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 18, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 17, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at