rs367746278
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_014191.4(SCN8A):c.992+10T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,565,734 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 0 hom. )
Consequence
SCN8A
NM_014191.4 intron
NM_014191.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.05
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=-0.5).
BP6
?
Variant 12-51701217-T-A is Benign according to our data. Variant chr12-51701217-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 383174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000335 (51/152354) while in subpopulation AMR AF= 0.000915 (14/15304). AF 95% confidence interval is 0.000642. There are 0 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 51 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN8A | NM_001330260.2 | c.992+10T>A | intron_variant | ENST00000627620.5 | |||
SCN8A | NM_014191.4 | c.992+10T>A | intron_variant | ENST00000354534.11 | |||
SCN8A | NM_001177984.3 | c.992+10T>A | intron_variant | ||||
SCN8A | NM_001369788.1 | c.992+10T>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.992+10T>A | intron_variant | 1 | NM_014191.4 | P4 | |||
SCN8A | ENST00000627620.5 | c.992+10T>A | intron_variant | 5 | NM_001330260.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000335 AC: 51AN: 152236Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000119 AC: 27AN: 226458Hom.: 0 AF XY: 0.0000488 AC XY: 6AN XY: 123028
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GnomAD4 exome AF: 0.0000325 AC: 46AN: 1413380Hom.: 0 Cov.: 24 AF XY: 0.0000214 AC XY: 15AN XY: 702304
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GnomAD4 genome ? AF: 0.000335 AC: 51AN: 152354Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17AN XY: 74504
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 18, 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. - |
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 28, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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