12-51706681-A-G
Position:
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_ModerateBP6_ModerateBS2
The NM_014191.4(SCN8A):āc.1601A>Gā(p.Asn534Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000698 in 1,432,488 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 (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000070 ( 0 hom. )
Consequence
SCN8A
NM_014191.4 missense
NM_014191.4 missense
Scores
5
8
Clinical Significance
Conservation
PhyloP100: 4.40
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 -7 ACMG points.
PP2
Missense variant where missense usually causes diseases, SCN8A
BP4
Computational evidence support a benign effect (MetaRNN=0.23127636).
BP6
Variant 12-51706681-A-G is Benign according to our data. Variant chr12-51706681-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 530522.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN8A | NM_001330260.2 | c.1601A>G | p.Asn534Ser | missense_variant | 11/27 | ENST00000627620.5 | |
SCN8A | NM_014191.4 | c.1601A>G | p.Asn534Ser | missense_variant | 11/27 | ENST00000354534.11 | |
SCN8A | NM_001177984.3 | c.1601A>G | p.Asn534Ser | missense_variant | 11/26 | ||
SCN8A | NM_001369788.1 | c.1601A>G | p.Asn534Ser | missense_variant | 11/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.1601A>G | p.Asn534Ser | missense_variant | 11/27 | 1 | NM_014191.4 | P4 | |
SCN8A | ENST00000627620.5 | c.1601A>G | p.Asn534Ser | missense_variant | 11/27 | 5 | NM_001330260.2 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000447 AC: 1AN: 223952Hom.: 0 AF XY: 0.00000824 AC XY: 1AN XY: 121304
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GnomAD4 exome AF: 0.00000698 AC: 10AN: 1432488Hom.: 0 Cov.: 31 AF XY: 0.0000113 AC XY: 8AN XY: 710134
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GnomAD4 genome Cov.: 32
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32
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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 | Jun 14, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;.;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
Polyphen
0.0080, 0.0030
.;B;.;.;B;.;.
Vest4
0.19, 0.18, 0.17, 0.17, 0.17
MutPred
Loss of solvent accessibility (P = 0.0111);Loss of solvent accessibility (P = 0.0111);Loss of solvent accessibility (P = 0.0111);Loss of solvent accessibility (P = 0.0111);Loss of solvent accessibility (P = 0.0111);Loss of solvent accessibility (P = 0.0111);.;
MVP
0.88
MPC
0.79
ClinPred
T
GERP RS
Varity_R
gMVP
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