rs369346315
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 1P and 11B. PP2BP4_ModerateBP6BS1BS2
The NM_014191.4(SCN8A):c.5879G>A(p.Arg1960Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000725 in 1,613,468 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. R1960L) 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 -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN8A | NM_001330260.2 | c.5879G>A | p.Arg1960Gln | missense_variant | 27/27 | ENST00000627620.5 | |
SCN8A | NM_014191.4 | c.5879G>A | p.Arg1960Gln | missense_variant | 27/27 | ENST00000354534.11 | |
SCN8A | NM_001177984.3 | c.5756G>A | p.Arg1919Gln | missense_variant | 26/26 | ||
SCN8A | NM_001369788.1 | c.5756G>A | p.Arg1919Gln | missense_variant | 26/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.5879G>A | p.Arg1960Gln | missense_variant | 27/27 | 1 | NM_014191.4 | P4 | |
SCN8A | ENST00000627620.5 | c.5879G>A | p.Arg1960Gln | missense_variant | 27/27 | 5 | NM_001330260.2 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000855 AC: 13AN: 152128Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000323 AC: 8AN: 247552Hom.: 0 AF XY: 0.0000372 AC XY: 5AN XY: 134436
GnomAD4 exome AF: 0.0000712 AC: 104AN: 1461340Hom.: 0 Cov.: 33 AF XY: 0.0000770 AC XY: 56AN XY: 726916
GnomAD4 genome AF: 0.0000855 AC: 13AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6AN XY: 74298
ClinVar
Submissions by phenotype
not provided Uncertain:3Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 01, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 31, 2019 | This variant is associated with the following publications: (PMID: 27875746) - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2023 | SCN8A: PP2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 27, 2022 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 25, 2017 | The p.R1960Q variant (also known as c.5879G>A), located in coding exon 26 of the SCN8A gene, results from a G to A substitution at nucleotide position 5879. The arginine at codon 1960 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Developmental and epileptic encephalopathy, 13 Benign:1
Benign, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Mar 08, 2019 | This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BS1,BS2. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at