Variant chr2-165139510-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_006922.4(SCN3A):c.2118G>A(p.Val706=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,613,952 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 31 hom. )

Consequence

SCN3A
NM_006922.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.99

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 2-165139510-C-T is Benign according to our data. Variant chr2-165139510-C-T is described in ClinVar as [Benign]. Clinvar id is 194396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-165139510-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.99 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00185 (281/152290) while in subpopulation EAS AF= 0.0253 (131/5174). AF 95% confidence interval is 0.0218. There are 1 homozygotes in gnomad4. There are 149 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 281 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN3A	NM_006922.4 linkuse as main transcript	c.2118G>A	p.Val706=	synonymous_variant	14/28	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.2118G>A	p.Val706=	synonymous_variant	14/28	1	NM_006922.4	ENSP00000283254	P1	Q9NY46-3

Frequencies

GnomAD3 genomes

AF:

0.00184

AC:

280

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.0253

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00109

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00350

AC:

878

AN:

251144

Hom.:

AF XY:

0.00345

AC XY:

468

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.0292

Gnomad SAS exome

AF:

0.00232

Gnomad FIN exome

AF:

0.00324

Gnomad NFE exome

AF:

0.00140

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00208

AC:

3036

AN:

1461662

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

1554

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000336

Gnomad4 ASJ exome

AF:

0.00165

Gnomad4 EAS exome

AF:

0.0315

Gnomad4 SAS exome

AF:

0.00245

Gnomad4 FIN exome

AF:

0.00264

Gnomad4 NFE exome

AF:

0.00109

Gnomad4 OTH exome

AF:

0.00242

GnomAD4 genome

AF:

0.00185

AC:

281

AN:

152290

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

149

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.0253

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00320

Gnomad4 NFE

AF:

0.00109

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00119

Hom.:

Bravo

AF:

0.00213

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.00107

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 08, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

May 04, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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