12-51745885-CTTT-C
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_014191.4(SCN8A):c.1999-7_1999-5del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000148 in 1,084,032 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
SCN8A
NM_014191.4 splice_polypyrimidine_tract, intron
NM_014191.4 splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.316
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 Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN8A | NM_001330260.2 | c.1999-7_1999-5del | splice_polypyrimidine_tract_variant, intron_variant | ENST00000627620.5 | |||
SCN8A | NM_014191.4 | c.1999-7_1999-5del | splice_polypyrimidine_tract_variant, intron_variant | ENST00000354534.11 | |||
SCN8A | NM_001177984.3 | c.1999-7_1999-5del | splice_polypyrimidine_tract_variant, intron_variant | ||||
SCN8A | NM_001369788.1 | c.1999-7_1999-5del | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.1999-7_1999-5del | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_014191.4 | P4 | |||
SCN8A | ENST00000627620.5 | c.1999-7_1999-5del | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001330260.2 | A1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
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31
GnomAD3 exomes AF: 0.0000499 AC: 4AN: 80108Hom.: 0 AF XY: 0.0000702 AC XY: 3AN XY: 42762
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GnomAD4 exome AF: 0.0000148 AC: 16AN: 1084032Hom.: 0 AF XY: 0.0000186 AC XY: 10AN XY: 538464
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GnomAD4 genome Cov.: 31
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31
ClinVar
Not reported inComputational scores
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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