12-51788268-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001330260.2(SCN8A):​c.4228-427A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.858 in 144,990 control chromosomes in the GnomAD database, including 53,565 homozygotes. 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: 𝑓 0.86 ( 53565 hom., cov: 21)

Consequence

SCN8A
NM_001330260.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.154
Variant links:
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.99).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SCN8ANM_001330260.2 linkc.4228-427A>G intron_variant Intron 22 of 26 ENST00000627620.5 NP_001317189.1 Q9UQD0-2Q6B4S4
SCN8ANM_014191.4 linkc.4228-427A>G intron_variant Intron 22 of 26 ENST00000354534.11 NP_055006.1 Q9UQD0-1
SCN8ANM_001177984.3 linkc.4105-427A>G intron_variant Intron 21 of 25 NP_001171455.1 Q9UQD0-5
SCN8ANM_001369788.1 linkc.4105-427A>G intron_variant Intron 21 of 25 NP_001356717.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SCN8AENST00000354534.11 linkc.4228-427A>G intron_variant Intron 22 of 26 1 NM_014191.4 ENSP00000346534.4 Q9UQD0-1
SCN8AENST00000627620.5 linkc.4228-427A>G intron_variant Intron 22 of 26 5 NM_001330260.2 ENSP00000487583.2 Q9UQD0-2
SCN8AENST00000599343.5 linkc.4261-427A>G intron_variant Intron 21 of 25 5 ENSP00000476447.3 Q9UQD0-3
SCN8AENST00000355133.7 linkc.4105-427A>G intron_variant Intron 20 of 24 1 ENSP00000347255.4 Q9UQD0-5

Frequencies

GnomAD3 genomes
AF:
0.858
AC:
124264
AN:
144876
Hom.:
53507
Cov.:
21
show subpopulations
Gnomad AFR
AF:
0.812
Gnomad AMI
AF:
0.946
Gnomad AMR
AF:
0.902
Gnomad ASJ
AF:
0.830
Gnomad EAS
AF:
0.976
Gnomad SAS
AF:
0.698
Gnomad FIN
AF:
0.901
Gnomad MID
AF:
0.811
Gnomad NFE
AF:
0.871
Gnomad OTH
AF:
0.875
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.858
AC:
124380
AN:
144990
Hom.:
53565
Cov.:
21
AF XY:
0.857
AC XY:
59958
AN XY:
69934
show subpopulations
Gnomad4 AFR
AF:
0.813
Gnomad4 AMR
AF:
0.903
Gnomad4 ASJ
AF:
0.830
Gnomad4 EAS
AF:
0.976
Gnomad4 SAS
AF:
0.699
Gnomad4 FIN
AF:
0.901
Gnomad4 NFE
AF:
0.871
Gnomad4 OTH
AF:
0.876
Alfa
AF:
0.872
Hom.:
9818
Bravo
AF:
0.864
Asia WGS
AF:
0.859
AC:
2983
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.99
CADD
Benign
1.4
DANN
Benign
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs167337; hg19: chr12-52182052; API