11-123642501-C-T

Position:

chr11-123642501-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001040151.2(SCN3B):c.390G>A(p.Ala130=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,614,168 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A130A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00078 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 4 hom. )

Consequence

SCN3B
NM_001040151.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -2.85

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 11-123642501-C-T is Benign according to our data. Variant chr11-123642501-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 139033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-123642501-C-T is described in Lovd as [Benign]. Variant chr11-123642501-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-2.85 with no splicing effect.

BS2

High AC in GnomAd4 at 119 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SCN3B	NM_001040151.2 linkuse as main transcript	c.390G>A	p.Ala130=	synonymous_variant	4/7	ENST00000299333.8
SCN3B	NM_018400.4 linkuse as main transcript	c.390G>A	p.Ala130=	synonymous_variant	3/6
SCN3B	XM_011542897.3 linkuse as main transcript	c.390G>A	p.Ala130=	synonymous_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN3B	ENST00000299333.8 linkuse as main transcript	c.390G>A	p.Ala130=	synonymous_variant	4/7	1	NM_001040151.2	P1

Frequencies

GnomAD3 genomes

AF:

0.000782

AC:

119

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000985

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000958

AC:

241

AN:

251438

Hom.:

AF XY:

0.00106

AC XY:

144

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.000893

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000947

Gnomad FIN exome

AF:

0.00323

Gnomad NFE exome

AF:

0.00103

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00111

AC:

1623

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

836

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.000918

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000823

Gnomad4 FIN exome

AF:

0.00296

Gnomad4 NFE exome

AF:

0.00117

Gnomad4 OTH exome

AF:

0.000729

GnomAD4 genome

AF:

0.000781

AC:

119

AN:

152274

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00292

Gnomad4 NFE

AF:

0.000985

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000467

Hom.:

Bravo

AF:

0.000514

EpiCase

AF:

0.00120

EpiControl

AF:

0.000711

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2022	SCN3B: BP4, BP7 -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 13, 2022	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 29, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Brugada syndrome 7

Benign:2

Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Feb 14, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Cardiovascular phenotype

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 28, 2015

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

5.8

DANN

Benign

0.77

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

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