rs919899554
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2
The NM_014191.4(SCN8A):c.4743C>T(p.Phe1581=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,882 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 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
SCN8A
NM_014191.4 synonymous
NM_014191.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.09
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 -8 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 12-51794589-C-T is Benign according to our data. Variant chr12-51794589-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 530564.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAdExome4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN8A | NM_001330260.2 | c.4743C>T | p.Phe1581= | synonymous_variant | 26/27 | ENST00000627620.5 | |
SCN8A | NM_014191.4 | c.4743C>T | p.Phe1581= | synonymous_variant | 26/27 | ENST00000354534.11 | |
SCN8A | NM_001177984.3 | c.4620C>T | p.Phe1540= | synonymous_variant | 25/26 | ||
SCN8A | NM_001369788.1 | c.4620C>T | p.Phe1540= | synonymous_variant | 25/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.4743C>T | p.Phe1581= | synonymous_variant | 26/27 | 1 | NM_014191.4 | P4 | |
SCN8A | ENST00000627620.5 | c.4743C>T | p.Phe1581= | synonymous_variant | 26/27 | 5 | NM_001330260.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461696Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727126
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74344
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 11, 2023 | - - |
Computational scores
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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