rs147205617

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_018400.4(SCN3B):c.328G>A(p.Val110Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000221 in 1,614,148 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V110V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 4 hom. )

Consequence

SCN3B
NM_018400.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:5B:6

Conservation

PhyloP100: 7.49

Publications

20 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.030202001).

BP6

Variant 11-123642563-C-T is Benign according to our data. Variant chr11-123642563-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 190886.

BS2

High AC in GnomAd4 at 48 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018400.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN3B	NM_001040151.2	MANE Select	c.328G>A	p.Val110Ile	missense	Exon 4 of 7	NP_001035241.1
	SCN3B	NM_018400.4		c.328G>A	p.Val110Ile	missense	Exon 3 of 6	NP_060870.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SCN3B	ENST00000299333.8	TSL:1 MANE Select	c.328G>A	p.Val110Ile	missense	Exon 4 of 7	ENSP00000299333.3
SCN3B	ENST00000392770.6	TSL:1	c.328G>A	p.Val110Ile	missense	Exon 3 of 6	ENSP00000376523.2
SCN3B	ENST00000530277.5	TSL:1	c.328G>A	p.Val110Ile	missense	Exon 4 of 6	ENSP00000432785.1

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00232

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000306

AC:

AN:

251476

AF XY:

0.000265

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00256

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000211

AC:

308

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

156

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00297

AC:

118

AN:

39698

South Asian (SAS)

AF:

0.000452

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000252

AC:

AN:

1111996

Other (OTH)

AF:

0.00189

AC:

114

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000315

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.000577

AC:

AN:

41560

American (AMR)

AF:

0.0000654

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00232

AC:

AN:

5166

South Asian (SAS)

AF:

0.000622

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68020

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000422

Hom.:

Bravo

AF:

0.000423

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000321

AC:

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

not specified (3)

Brugada syndrome 7 (1)

Cardiomyopathy (1)

Cardiovascular phenotype (1)

Death in infancy (1)

SCN3B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.37

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.37

MutationAssessor

Benign

1.9

PhyloP100

7.5

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.75

REVEL

Uncertain

0.38

Sift

Benign

0.14

Sift4G

Benign

0.15

Polyphen

1.0

Vest4

0.53

MVP

0.73

MPC

1.1

ClinPred

0.041

GERP RS

6.0

Varity_R

0.22

gMVP

0.81

Mutation Taster

=12/88

disease causing

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over