rs774383541
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_014191.4(SCN8A):c.1611G>A(p.Gly537=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000367 in 1,551,054 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 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
SCN8A
NM_014191.4 synonymous
NM_014191.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0430
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 -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
Variant 12-51706691-G-A is Benign according to our data. Variant chr12-51706691-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 530643.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.043 with no splicing effect.
BS2
?
High AC in GnomAd4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN8A | NM_001330260.2 | c.1611G>A | p.Gly537= | synonymous_variant | 11/27 | ENST00000627620.5 | |
SCN8A | NM_014191.4 | c.1611G>A | p.Gly537= | synonymous_variant | 11/27 | ENST00000354534.11 | |
SCN8A | NM_001177984.3 | c.1611G>A | p.Gly537= | synonymous_variant | 11/26 | ||
SCN8A | NM_001369788.1 | c.1611G>A | p.Gly537= | synonymous_variant | 11/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.1611G>A | p.Gly537= | synonymous_variant | 11/27 | 1 | NM_014191.4 | P4 | |
SCN8A | ENST00000627620.5 | c.1611G>A | p.Gly537= | synonymous_variant | 11/27 | 5 | NM_001330260.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152164Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000357 AC: 50AN: 1398890Hom.: 0 Cov.: 31 AF XY: 0.0000304 AC XY: 21AN XY: 691312
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74318
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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 | Dec 02, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at