2-165139597-T-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006922.4(SCN3A):c.2031A>T(p.Thr677Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 1,613,204 control chromosomes in the GnomAD database, including 173,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T677T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.52 ( 21573 hom., cov: 31)

Exomes 𝑓: 0.45 ( 151513 hom. )

Consequence

SCN3A
NM_006922.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0720

Publications

19 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 2-165139597-T-A is Benign according to our data. Variant chr2-165139597-T-A is described in ClinVar as Benign. ClinVar VariationId is 586501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.072 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN3A	NM_006922.4 link	c.2031A>T	p.Thr677Thr	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.2031A>T	p.Thr677Thr	synonymous_variant	Exon 14 of 28	1	NM_006922.4	ENSP00000283254.7		Q9NY46-3

Frequencies

GnomAD3 genomes

AF:

0.519

AC:

78818

AN:

151780

Hom.:

21544

Cov.:

show subpopulations

Gnomad AFR

AF:

0.663

Gnomad AMI

AF:

0.440

Gnomad AMR

AF:

0.562

Gnomad ASJ

AF:

0.503

Gnomad EAS

AF:

0.790

Gnomad SAS

AF:

0.587

Gnomad FIN

AF:

0.409

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.416

Gnomad OTH

AF:

0.512

GnomAD2 exomes

AF:

0.511

AC:

128191

AN:

250954

AF XY:

0.502

show subpopulations

Gnomad AFR exome

AF:

0.666

Gnomad AMR exome

AF:

0.624

Gnomad ASJ exome

AF:

0.495

Gnomad EAS exome

AF:

0.804

Gnomad FIN exome

AF:

0.408

Gnomad NFE exome

AF:

0.413

Gnomad OTH exome

AF:

0.478

GnomAD4 exome

AF:

0.448

AC:

653980

AN:

1461306

Hom.:

151513

Cov.:

AF XY:

0.450

AC XY:

326814

AN XY:

726970

show subpopulations

African (AFR)

AF:

0.663

AC:

22180

AN:

33446

American (AMR)

AF:

0.615

AC:

27471

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.499

AC:

13023

AN:

26124

East Asian (EAS)

AF:

0.729

AC:

28928

AN:

39682

South Asian (SAS)

AF:

0.567

AC:

48883

AN:

86250

European-Finnish (FIN)

AF:

0.410

AC:

21871

AN:

53370

Middle Eastern (MID)

AF:

0.510

AC:

2938

AN:

5764

European-Non Finnish (NFE)

AF:

0.414

AC:

459748

AN:

1111608

Other (OTH)

AF:

0.479

AC:

28938

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

19556

39113

58669

78226

97782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14528

29056

43584

58112

72640

<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:

0.519

AC:

78887

AN:

151898

Hom.:

21573

Cov.:

AF XY:

0.523

AC XY:

38796

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.662

AC:

27440

AN:

41426

American (AMR)

AF:

0.562

AC:

8564

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.503

AC:

1745

AN:

3468

East Asian (EAS)

AF:

0.791

AC:

4053

AN:

5126

South Asian (SAS)

AF:

0.587

AC:

2821

AN:

4808

European-Finnish (FIN)

AF:

0.409

AC:

4313

AN:

10548

Middle Eastern (MID)

AF:

0.531

AC:

156

AN:

294

European-Non Finnish (NFE)

AF:

0.416

AC:

28304

AN:

67966

Other (OTH)

AF:

0.518

AC:

1093

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1847

3693

5540

7386

9233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

682

1364

2046

2728

3410

<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:

0.447

Hom.:

5057

Bravo

AF:

0.540

Asia WGS

AF:

0.696

AC:

2419

AN:

3478

EpiCase

AF:

0.422

EpiControl

AF:

0.420

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 13, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 76% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 71. Only high quality variants are reported. -

Epilepsy, familial focal, with variable foci 4

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Developmental and epileptic encephalopathy, 62

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

-0.072

Mutation Taster

=79/21

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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