rs373221046
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_014191.4(SCN8A):c.3491-10C>T 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 0.00000378 in 1,585,962 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 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
SCN8A
NM_014191.4 splice_polypyrimidine_tract, intron
NM_014191.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.02657
2
Clinical Significance
Conservation
PhyloP100: 0.0840
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.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
Variant 12-51770519-C-T is Benign according to our data. Variant chr12-51770519-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 436669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN8A | NM_001330260.2 | c.3491-10C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000627620.5 | |||
SCN8A | NM_014191.4 | c.3491-10C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000354534.11 | |||
SCN8A | NM_001177984.3 | c.3491-10C>T | splice_polypyrimidine_tract_variant, intron_variant | ||||
SCN8A | NM_001369788.1 | c.3491-10C>T | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.3491-10C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_014191.4 | P4 | |||
SCN8A | ENST00000627620.5 | c.3491-10C>T | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001330260.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152182Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000471 AC: 1AN: 212404Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 114556
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GnomAD4 exome AF: 6.97e-7 AC: 1AN: 1433780Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1AN XY: 709812
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74340
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 11, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 14, 2016 | - - |
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at