NM_006922.4:c.2118G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_006922.4(SCN3A):c.2118G>A(p.Val706Val) 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

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina, ClinGen
developmental and epileptic encephalopathy, 62
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
epilepsy, familial focal, with variable foci 4
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SCN3A links:

ENSG00000236283 (HGNC:):

ENSG00000236283 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 194396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 281 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN3A	NM_006922.4 link	c.2118G>A	p.Val706Val	synonymous_variant	Exon 14 of 28	ENST00000283254.12	NP_008853.3	Q9NY46-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN3A	ENST00000283254.12 link	c.2118G>A	p.Val706Val	synonymous_variant	Exon 14 of 28	1	NM_006922.4	ENSP00000283254.7		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

GnomAD2 exomes

AF:

0.00350

AC:

878

AN:

251144

AF XY:

0.00345

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 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

African (AFR)

AF:

0.000269

AC:

AN:

33462

American (AMR)

AF:

0.000336

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00165

AC:

AN:

26128

East Asian (EAS)

AF:

0.0315

AC:

1252

AN:

39686

South Asian (SAS)

AF:

0.00245

AC:

211

AN:

86256

European-Finnish (FIN)

AF:

0.00264

AC:

141

AN:

53402

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00109

AC:

1214

AN:

1111872

Other (OTH)

AF:

0.00242

AC:

146

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

171

342

512

683

854

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00185

AC:

281

AN:

152290

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

149

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41574

American (AMR)

AF:

0.000458

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3470

East Asian (EAS)

AF:

0.0253

AC:

131

AN:

5174

South Asian (SAS)

AF:

0.00186

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00320

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00109

AC:

AN:

68018

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Jul 08, 2019

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

May 04, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

2.0

Mutation Taster

=58/42

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over