rs303808

Positions:

Variant summary

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

The NM_001330260.2(SCN8A):c.3490+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 1,513,632 control chromosomes in the GnomAD database, including 516,757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 45915 hom., cov: 32)

Exomes 𝑓: 0.83 ( 470842 hom. )

Consequence

SCN8A
NM_001330260.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.162

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:

SCN8A (HGNC:):

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=-0.83).

BP6

Variant 12-51770005-G-A is Benign according to our data. Variant chr12-51770005-G-A is described in ClinVar as [Benign]. Clinvar id is 260352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-51770005-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
SCN8A	NM_001330260.2 linkuse as main transcript	c.3490+20G>A	intron_variant	ENST00000627620.5	NP_001317189.1	Q9UQD0-2Q6B4S4
SCN8A	NM_014191.4 linkuse as main transcript	c.3490+20G>A	intron_variant	ENST00000354534.11	NP_055006.1	Q9UQD0-1
SCN8A	NM_001177984.3 linkuse as main transcript	c.3490+20G>A	intron_variant		NP_001171455.1	Q9UQD0-5
SCN8A	NM_001369788.1 linkuse as main transcript	c.3490+20G>A	intron_variant		NP_001356717.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SCN8A	ENST00000354534.11 linkuse as main transcript	c.3490+20G>A	intron_variant	1	NM_014191.4	ENSP00000346534.4	Q9UQD0-1
SCN8A	ENST00000627620.5 linkuse as main transcript	c.3490+20G>A	intron_variant	5	NM_001330260.2	ENSP00000487583.2	Q9UQD0-2
SCN8A	ENST00000599343.5 linkuse as main transcript	c.3523+20G>A	intron_variant	5		ENSP00000476447.3	Q9UQD0-3
SCN8A	ENST00000355133.7 linkuse as main transcript	c.3490+20G>A	intron_variant	1		ENSP00000347255.4	Q9UQD0-5

Frequencies

GnomAD3 genomes

AF:

0.764

AC:

116093

AN:

152016

Hom.:

45904

Cov.:

show subpopulations

Gnomad AFR

AF:

0.552

Gnomad AMI

AF:

0.886

Gnomad AMR

AF:

0.853

Gnomad ASJ

AF:

0.802

Gnomad EAS

AF:

0.891

Gnomad SAS

AF:

0.576

Gnomad FIN

AF:

0.900

Gnomad MID

AF:

0.717

Gnomad NFE

AF:

0.850

Gnomad OTH

AF:

0.792

GnomAD3 exomes

AF:

0.807

AC:

147815

AN:

183064

Hom.:

60920

AF XY:

0.795

AC XY:

77060

AN XY:

96872

show subpopulations

Gnomad AFR exome

AF:

0.559

Gnomad AMR exome

AF:

0.888

Gnomad ASJ exome

AF:

0.821

Gnomad EAS exome

AF:

0.885

Gnomad SAS exome

AF:

0.571

Gnomad FIN exome

AF:

0.902

Gnomad NFE exome

AF:

0.847

Gnomad OTH exome

AF:

0.815

GnomAD4 exome

AF:

0.828

AC:

1126696

AN:

1361498

Hom.:

470842

Cov.:

AF XY:

0.820

AC XY:

554263

AN XY:

676000

show subpopulations

Gnomad4 AFR exome

AF:

0.548

Gnomad4 AMR exome

AF:

0.882

Gnomad4 ASJ exome

AF:

0.821

Gnomad4 EAS exome

AF:

0.903

Gnomad4 SAS exome

AF:

0.573

Gnomad4 FIN exome

AF:

0.899

Gnomad4 NFE exome

AF:

0.848

Gnomad4 OTH exome

AF:

0.815

GnomAD4 genome

AF:

0.763

AC:

116137

AN:

152134

Hom.:

45915

Cov.:

AF XY:

0.763

AC XY:

56797

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.552

Gnomad4 AMR

AF:

0.854

Gnomad4 ASJ

AF:

0.802

Gnomad4 EAS

AF:

0.891

Gnomad4 SAS

AF:

0.577

Gnomad4 FIN

AF:

0.900

Gnomad4 NFE

AF:

0.850

Gnomad4 OTH

AF:

0.787

Alfa

AF:

0.822

Hom.:

70873

Bravo

AF:

0.757

Asia WGS

AF:

0.685

AC:

2378

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 96% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 89. Only high quality variants are reported. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Cognitive impairment with or without cerebellar ataxia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Early infantile epileptic encephalopathy with suppression bursts

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Seizures, benign familial infantile, 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Myoclonus, familial, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Developmental and epileptic encephalopathy, 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.86

DANN

Benign

0.31

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.

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