12-51769464-A-G
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_014191.4(SCN8A):c.3372+129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 648,914 control chromosomes in the GnomAD database, including 214,441 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.74 ( 43794 hom., cov: 30)
Exomes 𝑓: 0.82 ( 170647 hom. )
Consequence
SCN8A
NM_014191.4 intron
NM_014191.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.111
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 Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 12-51769464-A-G is Benign according to our data. Variant chr12-51769464-A-G is described in ClinVar as [Benign]. Clinvar id is 669362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN8A | NM_001330260.2 | c.3372+129A>G | intron_variant | ENST00000627620.5 | |||
SCN8A | NM_014191.4 | c.3372+129A>G | intron_variant | ENST00000354534.11 | |||
SCN8A | NM_001177984.3 | c.3372+129A>G | intron_variant | ||||
SCN8A | NM_001369788.1 | c.3372+129A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.3372+129A>G | intron_variant | 1 | NM_014191.4 | P4 | |||
SCN8A | ENST00000627620.5 | c.3372+129A>G | intron_variant | 5 | NM_001330260.2 | A1 |
Frequencies
GnomAD3 genomes AF: 0.737 AC: 111874AN: 151884Hom.: 43795 Cov.: 30
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GnomAD4 exome AF: 0.822 AC: 408302AN: 496912Hom.: 170647 AF XY: 0.811 AC XY: 210543AN XY: 259678
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GnomAD4 genome AF: 0.736 AC: 111893AN: 152002Hom.: 43794 Cov.: 30 AF XY: 0.738 AC XY: 54877AN XY: 74330
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jul 15, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 27% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 25. Only high quality variants are reported. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2018 | 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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at