rs1275085

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001040151.2(SCN3B):c.438C>T(p.Thr146Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0859 in 1,613,836 control chromosomes in the GnomAD database, including 6,568 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. T146T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.088 ( 648 hom., cov: 32)

Exomes 𝑓: 0.086 ( 5920 hom. )

Consequence

SCN3B
NM_001040151.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.06

Publications

13 publications found

Variant links:

Genes affected

SCN3B (HGNC:20665): (sodium voltage-gated channel beta subunit 3) Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit 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 beta subunit gene family, and influences the inactivation kinetics of the sodium channel. Two alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

SCN3B Gene-Disease associations (from GenCC):

familial atrial fibrillation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Brugada syndrome 7
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
Brugada syndrome 1
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

SCN3B 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=-0.45).

BP6

Variant 11-123642453-G-A is Benign according to our data. Variant chr11-123642453-G-A is described in ClinVar as Benign. ClinVar VariationId is 261028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN3B	NM_001040151.2 link	c.438C>T	p.Thr146Thr	synonymous_variant	Exon 4 of 7	ENST00000299333.8	NP_001035241.1	Q9NY72A0A024R3H7
SCN3B	NM_018400.4 link	c.438C>T	p.Thr146Thr	synonymous_variant	Exon 3 of 6		NP_060870.1	Q9NY72A0A024R3H7
SCN3B	XM_011542897.3 link	c.438C>T	p.Thr146Thr	synonymous_variant	Exon 4 of 7		XP_011541199.1	Q9NY72A0A024R3H7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN3B	ENST00000299333.8 link	c.438C>T	p.Thr146Thr	synonymous_variant	Exon 4 of 7	1	NM_001040151.2	ENSP00000299333.3		Q9NY72

Frequencies

GnomAD3 genomes

AF:

0.0882

AC:

13401

AN:

152002

Hom.:

647

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0962

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.0540

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.00290

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.0951

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.0877

Gnomad OTH

AF:

0.0904

GnomAD2 exomes

AF:

0.0864

AC:

21697

AN:

251046

AF XY:

0.0920

show subpopulations

Gnomad AFR exome

AF:

0.0967

Gnomad AMR exome

AF:

0.0380

Gnomad ASJ exome

AF:

0.133

Gnomad EAS exome

AF:

0.00261

Gnomad FIN exome

AF:

0.0930

Gnomad NFE exome

AF:

0.0881

Gnomad OTH exome

AF:

0.0944

GnomAD4 exome

AF:

0.0856

AC:

125191

AN:

1461716

Hom.:

5920

Cov.:

AF XY:

0.0883

AC XY:

64235

AN XY:

727182

show subpopulations

African (AFR)

AF:

0.0956

AC:

3200

AN:

33474

American (AMR)

AF:

0.0410

AC:

1835

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

3492

AN:

26136

East Asian (EAS)

AF:

0.00181

AC:

AN:

39700

South Asian (SAS)

AF:

0.157

AC:

13505

AN:

86246

European-Finnish (FIN)

AF:

0.0916

AC:

4891

AN:

53412

Middle Eastern (MID)

AF:

0.122

AC:

706

AN:

5764

European-Non Finnish (NFE)

AF:

0.0830

AC:

92283

AN:

1111874

Other (OTH)

AF:

0.0862

AC:

5207

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

6586

13172

19758

26344

32930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3412

6824

10236

13648

17060

<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:

0.0881

AC:

13401

AN:

152120

Hom.:

648

Cov.:

AF XY:

0.0892

AC XY:

6635

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.0960

AC:

3984

AN:

41498

American (AMR)

AF:

0.0539

AC:

824

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

487

AN:

3470

East Asian (EAS)

AF:

0.00291

AC:

AN:

5160

South Asian (SAS)

AF:

0.157

AC:

755

AN:

4812

European-Finnish (FIN)

AF:

0.0951

AC:

1008

AN:

10602

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0878

AC:

5965

AN:

67974

Other (OTH)

AF:

0.0890

AC:

188

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

613

1227

1840

2454

3067

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<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:

0.0861

Hom.:

1370

Bravo

AF:

0.0835

Asia WGS

AF:

0.0610

AC:

214

AN:

3478

EpiCase

AF:

0.0932

EpiControl

AF:

0.0925

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 09, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

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

- -

Cardiovascular phenotype

Benign:1

Jun 23, 2015

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Brugada syndrome 7

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.45

CADD

Benign

5.9

(source)

DANN

Benign

0.86

PhyloP100

-1.1

Mutation Taster

=100/0

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

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