rs117217073
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2
The NM_014191.4(SCN8A):c.3076C>T(p.Arg1026Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,613,932 control chromosomes in the GnomAD database, including 183 homozygotes. 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. R1026H) has been classified as Uncertain significance.
Frequency
Consequence
NM_014191.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN8A | NM_001330260.2 | c.3076C>T | p.Arg1026Cys | missense_variant | 17/27 | ENST00000627620.5 | |
SCN8A | NM_014191.4 | c.3076C>T | p.Arg1026Cys | missense_variant | 17/27 | ENST00000354534.11 | |
SCN8A | NM_001177984.3 | c.3076C>T | p.Arg1026Cys | missense_variant | 17/26 | ||
SCN8A | NM_001369788.1 | c.3076C>T | p.Arg1026Cys | missense_variant | 17/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.3076C>T | p.Arg1026Cys | missense_variant | 17/27 | 1 | NM_014191.4 | P4 | |
SCN8A | ENST00000627620.5 | c.3076C>T | p.Arg1026Cys | missense_variant | 17/27 | 5 | NM_001330260.2 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0107 AC: 1630AN: 152158Hom.: 16 Cov.: 32
GnomAD3 exomes AF: 0.0117 AC: 2916AN: 249052Hom.: 33 AF XY: 0.0119 AC XY: 1604AN XY: 135122
GnomAD4 exome AF: 0.0127 AC: 18504AN: 1461656Hom.: 167 Cov.: 31 AF XY: 0.0127 AC XY: 9228AN XY: 727102
GnomAD4 genome AF: 0.0107 AC: 1629AN: 152276Hom.: 16 Cov.: 32 AF XY: 0.0118 AC XY: 879AN XY: 74454
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 25, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | SCN8A: PP2, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 08, 2019 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Developmental and epileptic encephalopathy, 13 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory of Inherited Metabolic Diseases, Research centre for medical genetics | Feb 14, 2020 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 06, 2016 | This alteration is classified as 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 | Feb 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at