chr11-123634162-G-A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_001040151.2(SCN3B):c.629C>T(p.Ala210Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,613,600 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00053 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

SCN3B
NM_001040151.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.714

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 11-123634162-G-A is Benign according to our data. Variant chr11-123634162-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 190884.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=1}.

BS2

High AC in GnomAd4 at 81 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN3B	NM_001040151.2 link	c.629C>T	p.Ala210Val	missense_variant	Exon 6 of 7	ENST00000299333.8	NP_001035241.1	Q9NY72A0A024R3H7
SCN3B	NM_018400.4 link	c.629C>T	p.Ala210Val	missense_variant	Exon 5 of 6		NP_060870.1	Q9NY72A0A024R3H7
SCN3B	XM_011542897.3 link	c.629C>T	p.Ala210Val	missense_variant	Exon 6 of 7		XP_011541199.1	Q9NY72A0A024R3H7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN3B	ENST00000299333.8 link	c.629C>T	p.Ala210Val	missense_variant	Exon 6 of 7	1	NM_001040151.2	ENSP00000299333.3		Q9NY72

Frequencies

GnomAD3 genomes

AF:

0.000533

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00718

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000370

AC:

AN:

251368

Hom.:

AF XY:

0.000368

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00421

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000138

AC:

202

AN:

1461418

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

107

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00347

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.000532

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.000874

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00718

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000582

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.000272

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jul 30, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Has not been previously published as pathogenic or benign to our knowledge; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; In silico analysis indicates that this missense variant does not alter protein structure/function; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (PMID: 25741868) -

Cardiovascular phenotype

Benign:1

Mar 03, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely 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

Oct 15, 2024

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

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.039

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.40

T;T;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.75

.;T;.

M_CAP

Benign

0.028

MetaRNN

Benign

0.0070

T;T;T

MetaSVM

Uncertain

-0.13

MutationAssessor

Benign

1.1

L;L;L

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.29

Sift

Benign

0.27

T;T;T

Sift4G

Benign

0.17

T;T;T

Polyphen

0.0020

B;B;B

Vest4

0.13

MVP

0.62

MPC

0.42

ClinPred

0.042

GERP RS

0.80

Varity_R

0.045

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.27

Position offset: -41

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over