12-51745885-C-CT
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_014191.4(SCN8A):c.1999-5dup 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 0.0709 in 1,061,912 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0023 ( 0 hom., cov: 31)
Exomes 𝑓: 0.082 ( 2 hom. )
Consequence
SCN8A
NM_014191.4 splice_polypyrimidine_tract, intron
NM_014191.4 splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
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 Benign. Variant got -16 ACMG points.
BP6
Variant 12-51745885-C-CT is Benign according to our data. Variant chr12-51745885-C-CT is described in ClinVar as [Benign]. Clinvar id is 1294100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.098 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN8A | NM_001330260.2 | c.1999-5dup | splice_polypyrimidine_tract_variant, intron_variant | ENST00000627620.5 | |||
SCN8A | NM_014191.4 | c.1999-5dup | splice_polypyrimidine_tract_variant, intron_variant | ENST00000354534.11 | |||
SCN8A | NM_001177984.3 | c.1999-5dup | splice_polypyrimidine_tract_variant, intron_variant | ||||
SCN8A | NM_001369788.1 | c.1999-5dup | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.1999-5dup | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_014191.4 | P4 | |||
SCN8A | ENST00000627620.5 | c.1999-5dup | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001330260.2 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00230 AC: 329AN: 142782Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0969 AC: 7760AN: 80108Hom.: 0 AF XY: 0.0980 AC XY: 4189AN XY: 42762
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GnomAD4 exome AF: 0.0815 AC: 74942AN: 919090Hom.: 2 Cov.: 0 AF XY: 0.0813 AC XY: 37293AN XY: 458990
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GnomAD4 genome AF: 0.00233 AC: 333AN: 142822Hom.: 0 Cov.: 31 AF XY: 0.00245 AC XY: 170AN XY: 69418
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 06, 2019 | - - |
Computational 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