rs1490133991
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 8P and 4B. PVS1BS2
The NM_014191.4(SCN8A):c.618T>A(p.Tyr206Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000103 in 1,460,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
SCN8A
NM_014191.4 stop_gained
NM_014191.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 6.27
Genes affected
SCN8A (HGNC:10596): (sodium voltage-gated channel alpha subunit 8) This gene encodes a member of the sodium channel alpha subunit gene family. The encoded protein forms the ion pore region of the voltage-gated sodium channel. This protein is essential for the rapid membrane depolarization that occurs during the formation of the action potential in excitable neurons. Mutations in this gene are associated with cognitive disability, pancerebellar atrophy and ataxia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
BS2
High AC in GnomAdExome4 at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN8A | NM_014191.4 | c.618T>A | p.Tyr206Ter | stop_gained | 6/27 | ENST00000354534.11 | |
SCN8A | NM_001330260.2 | c.615-244T>A | intron_variant | ENST00000627620.5 | |||
SCN8A | NM_001177984.3 | c.618T>A | p.Tyr206Ter | stop_gained | 6/26 | ||
SCN8A | NM_001369788.1 | c.615-244T>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.618T>A | p.Tyr206Ter | stop_gained | 6/27 | 1 | NM_014191.4 | P4 | |
SCN8A | ENST00000627620.5 | c.615-244T>A | intron_variant | 5 | NM_001330260.2 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249790Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135462
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1460618Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10AN XY: 726682
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GnomAD4 genome Cov.: 32
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32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | May 03, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;D
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at