rs9943809

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001330260.2(SCN8A):c.4281+13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,603,488 control chromosomes in the GnomAD database, including 12,285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.090 ( 1020 hom., cov: 31)

Exomes 𝑓: 0.10 ( 11265 hom. )

Consequence

SCN8A
NM_001330260.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.432

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]

SCN8A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 12-51788761-A-G is Benign according to our data. Variant chr12-51788761-A-G is described in ClinVar as [Benign]. Clinvar id is 139073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-51788761-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SCN8A	NM_001330260.2 link	c.4281+13A>G	intron_variant	Intron 23 of 26	ENST00000627620.5	NP_001317189.1	Q9UQD0-2Q6B4S4
SCN8A	NM_014191.4 link	c.4281+13A>G	intron_variant	Intron 23 of 26	ENST00000354534.11	NP_055006.1	Q9UQD0-1
SCN8A	NM_001177984.3 link	c.4158+13A>G	intron_variant	Intron 22 of 25		NP_001171455.1	Q9UQD0-5
SCN8A	NM_001369788.1 link	c.4158+13A>G	intron_variant	Intron 22 of 25		NP_001356717.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCN8A	ENST00000354534.11 link	c.4281+13A>G	intron_variant	Intron 23 of 26	1	NM_014191.4	ENSP00000346534.4	Q9UQD0-1
SCN8A	ENST00000627620.5 link	c.4281+13A>G	intron_variant	Intron 23 of 26	5	NM_001330260.2	ENSP00000487583.2	Q9UQD0-2
SCN8A	ENST00000599343.5 link	c.4314+13A>G	intron_variant	Intron 22 of 25	5		ENSP00000476447.3	Q9UQD0-3
SCN8A	ENST00000355133.7 link	c.4158+13A>G	intron_variant	Intron 21 of 24	1		ENSP00000347255.4	Q9UQD0-5

Frequencies

GnomAD3 genomes

AF:

0.0902

AC:

13712

AN:

151976

Hom.:

1023

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0230

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.0964

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.364

Gnomad SAS

AF:

0.223

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0836

Gnomad OTH

AF:

0.0832

GnomAD3 exomes

AF:

0.133

AC:

32426

AN:

244588

Hom.:

3025

AF XY:

0.135

AC XY:

17786

AN XY:

132166

show subpopulations

Gnomad AFR exome

AF:

0.0196

Gnomad AMR exome

AF:

0.141

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.356

Gnomad SAS exome

AF:

0.211

Gnomad FIN exome

AF:

0.170

Gnomad NFE exome

AF:

0.0846

Gnomad OTH exome

AF:

0.116

GnomAD4 exome

AF:

0.103

AC:

150049

AN:

1451394

Hom.:

11265

Cov.:

AF XY:

0.106

AC XY:

76578

AN XY:

721496

show subpopulations

Gnomad4 AFR exome

AF:

0.0203

Gnomad4 AMR exome

AF:

0.135

Gnomad4 ASJ exome

AF:

0.131

Gnomad4 EAS exome

AF:

0.426

Gnomad4 SAS exome

AF:

0.207

Gnomad4 FIN exome

AF:

0.158

Gnomad4 NFE exome

AF:

0.0822

Gnomad4 OTH exome

AF:

0.104

GnomAD4 genome

AF:

0.0901

AC:

13701

AN:

152094

Hom.:

1020

Cov.:

AF XY:

0.0988

AC XY:

7345

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0229

Gnomad4 AMR

AF:

0.0964

Gnomad4 ASJ

AF:

0.139

Gnomad4 EAS

AF:

0.364

Gnomad4 SAS

AF:

0.222

Gnomad4 FIN

AF:

0.182

Gnomad4 NFE

AF:

0.0836

Gnomad4 OTH

AF:

0.0823

Alfa

AF:

0.0830

Hom.:

223

Bravo

AF:

0.0817

Asia WGS

AF:

0.251

AC:

871

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 01, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Early infantile epileptic encephalopathy with suppression bursts

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.2

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over