chr12-51662860-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_014191.4(SCN8A):c.43A>C(p.Lys15Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Consequence
SCN8A
NM_014191.4 missense
NM_014191.4 missense
Scores
9
4
Clinical Significance
Conservation
PhyloP100: 2.28
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, SCN8A
BP4
?
Computational evidence support a benign effect (MetaRNN=0.32702833).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN8A | NM_001330260.2 | c.43A>C | p.Lys15Gln | missense_variant | 2/27 | ENST00000627620.5 | |
SCN8A | NM_014191.4 | c.43A>C | p.Lys15Gln | missense_variant | 2/27 | ENST00000354534.11 | |
SCN8A | NM_001177984.3 | c.43A>C | p.Lys15Gln | missense_variant | 2/26 | ||
SCN8A | NM_001369788.1 | c.43A>C | p.Lys15Gln | missense_variant | 2/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN8A | ENST00000354534.11 | c.43A>C | p.Lys15Gln | missense_variant | 2/27 | 1 | NM_014191.4 | P4 | |
SCN8A | ENST00000627620.5 | c.43A>C | p.Lys15Gln | missense_variant | 2/27 | 5 | NM_001330260.2 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Coffin-Siris syndrome 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Nov 04, 2022 | ACMG classification criteria: PM2 moderated, PP2 supporting - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;.;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
Polyphen
0.32
.;B;.;.;.;.
Vest4
0.23, 0.28, 0.31, 0.30, 0.30
MutPred
Loss of methylation at K15 (P = 2e-04);Loss of methylation at K15 (P = 2e-04);Loss of methylation at K15 (P = 2e-04);Loss of methylation at K15 (P = 2e-04);Loss of methylation at K15 (P = 2e-04);Loss of methylation at K15 (P = 2e-04);
MVP
0.86
MPC
1.1
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.