rs116682517

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.552G>A(p.Thr184Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,613,714 control chromosomes in the GnomAD database, including 157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 13 hom., cov: 32)

Exomes 𝑓: 0.012 ( 144 hom. )

Consequence

SCN3A
NM_006922.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.895

Publications

5 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=-0.44).

BP6

Variant 2-165164442-C-T is Benign according to our data. Variant chr2-165164442-C-T is described in ClinVar as Benign. ClinVar VariationId is 240714.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.895 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00847 (1290/152218) while in subpopulation NFE AF = 0.0129 (875/68010). AF 95% confidence interval is 0.0122. There are 13 homozygotes in GnomAd4. There are 570 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1290 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN3A	NM_006922.4 link	c.552G>A	p.Thr184Thr	synonymous_variant	Exon 6 of 28	ENST00000283254.12	NP_008853.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN3A	ENST00000283254.12 link	c.552G>A	p.Thr184Thr	synonymous_variant	Exon 6 of 28	1	NM_006922.4	ENSP00000283254.7

Frequencies

GnomAD3 genomes

AF:

0.00848

AC:

1290

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00754

Gnomad ASJ

AF:

0.0228

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0104

Gnomad FIN

AF:

0.00434

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0129

Gnomad OTH

AF:

0.0148

GnomAD2 exomes

AF:

0.0101

AC:

2538

AN:

251184

AF XY:

0.0105

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00475

Gnomad ASJ exome

AF:

0.0205

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00388

Gnomad NFE exome

AF:

0.0145

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.0123

AC:

18027

AN:

1461496

Hom.:

144

Cov.:

AF XY:

0.0123

AC XY:

8975

AN XY:

727042

show subpopulations

African (AFR)

AF:

0.00209

AC:

AN:

33462

American (AMR)

AF:

0.00537

AC:

240

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.0198

AC:

516

AN:

26116

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39624

South Asian (SAS)

AF:

0.0104

AC:

898

AN:

86244

European-Finnish (FIN)

AF:

0.00567

AC:

303

AN:

53412

Middle Eastern (MID)

AF:

0.0125

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0137

AC:

15243

AN:

1111788

Other (OTH)

AF:

0.0113

AC:

684

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

956

1912

2867

3823

4779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.00847

AC:

1290

AN:

152218

Hom.:

Cov.:

AF XY:

0.00766

AC XY:

570

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.00221

AC:

AN:

41552

American (AMR)

AF:

0.00753

AC:

115

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0228

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.0104

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00434

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0129

AC:

875

AN:

68010

Other (OTH)

AF:

0.0147

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

131

196

262

327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0116

Hom.:

Bravo

AF:

0.00842

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0151

EpiControl

AF:

0.0164

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SCN3A: BP4, BP7, BS1, BS2 -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 21, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.44

CADD

Benign

5.5

(source)

DANN

Benign

0.82

PhyloP100

-0.90

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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