Variant 2-165164383-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006922.4(SCN3A):c.602+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,613,110 control chromosomes in the GnomAD database, including 26,558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5076 hom., cov: 32)

Exomes 𝑓: 0.15 ( 21482 hom. )

Consequence

SCN3A
NM_006922.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.134

Variant links:

Genes affected

SCN3A (HGNC:10590): (sodium voltage-gated channel alpha subunit 3) Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with 24 transmembrane domains and one or more regulatory beta subunits. They are responsible for the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family, and is found in a cluster of five alpha subunit genes on chromosome 2. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SCN3A links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 2-165164383-G-A is Benign according to our data. Variant chr2-165164383-G-A is described in ClinVar as [Benign]. Clinvar id is 586504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN3A	NM_006922.4 linkuse as main transcript	c.602+9C>T		intron_variant		ENST00000283254.12	NP_008853.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN3A	ENST00000283254.12 linkuse as main transcript	c.602+9C>T		intron_variant		1	NM_006922.4	ENSP00000283254	P1	Q9NY46-3

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34267

AN:

151794

Hom.:

5051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.361

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.521

Gnomad SAS

AF:

0.191

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.218

GnomAD3 exomes

AF:

0.219

AC:

54929

AN:

251052

Hom.:

8344

AF XY:

0.205

AC XY:

27886

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.370

Gnomad AMR exome

AF:

0.373

Gnomad ASJ exome

AF:

0.134

Gnomad EAS exome

AF:

0.535

Gnomad SAS exome

AF:

0.186

Gnomad FIN exome

AF:

0.228

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.182

GnomAD4 exome

AF:

0.146

AC:

213102

AN:

1461198

Hom.:

21482

Cov.:

AF XY:

0.145

AC XY:

105536

AN XY:

726914

show subpopulations

Gnomad4 AFR exome

AF:

0.369

Gnomad4 AMR exome

AF:

0.359

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.484

Gnomad4 SAS exome

AF:

0.186

Gnomad4 FIN exome

AF:

0.227

Gnomad4 NFE exome

AF:

0.110

Gnomad4 OTH exome

AF:

0.176

GnomAD4 genome

AF:

0.226

AC:

34339

AN:

151912

Hom.:

5076

Cov.:

AF XY:

0.232

AC XY:

17252

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.361

Gnomad4 AMR

AF:

0.287

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.521

Gnomad4 SAS

AF:

0.191

Gnomad4 FIN

AF:

0.232

Gnomad4 NFE

AF:

0.115

Gnomad4 OTH

AF:

0.228

Alfa

AF:

0.137

Hom.:

4054

Bravo

AF:

0.242

Asia WGS

AF:

0.370

AC:

1282

AN:

3478

EpiCase

AF:

0.108

EpiControl

AF:

0.105

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

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 35% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 33. Only high quality variants are reported. -

Epilepsy, familial focal, with variable foci 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Developmental and epileptic encephalopathy, 62

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

-0.78

CADD

Benign

DANN

Benign

0.75

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