rs770747359
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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.3373-9C>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 0.0000607 in 1,565,760 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 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000055 ( 0 hom. )
Consequence
SCN8A
NM_014191.4 splice_polypyrimidine_tract, intron
NM_014191.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00003172
2
Clinical Significance
Conservation
PhyloP100: -0.612
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=-0.81).
BP6
?
Variant 12-51769859-C-T is Benign according to our data. Variant chr12-51769859-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 530519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-51769859-C-T is described in Lovd as [Likely_benign].
BS2
?
High AC in GnomAd4 at 17 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN8A | NM_001330260.2 | c.3373-9C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000627620.5 | |||
SCN8A | NM_014191.4 | c.3373-9C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000354534.11 | |||
SCN8A | NM_001177984.3 | c.3373-9C>T | splice_polypyrimidine_tract_variant, intron_variant | ||||
SCN8A | NM_001369788.1 | c.3373-9C>T | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.3373-9C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_014191.4 | P4 | |||
SCN8A | ENST00000627620.5 | c.3373-9C>T | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001330260.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152102Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000444 AC: 9AN: 202830Hom.: 0 AF XY: 0.0000463 AC XY: 5AN XY: 108044
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GnomAD4 exome AF: 0.0000552 AC: 78AN: 1413658Hom.: 0 Cov.: 28 AF XY: 0.0000599 AC XY: 42AN XY: 700894
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GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152102Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74294
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ClinVar
Significance: Benign/Likely 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 | Jul 25, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 16, 2020 | - - |
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