Variant 3-179243250-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_171830.2(KCNMB3):c.482A>G(p.Asn161Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0492 in 1,317,818 control chromosomes in the GnomAD database, including 1,859 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 223 hom., cov: 30)

Exomes 𝑓: 0.049 ( 1636 hom. )

Consequence

KCNMB3
NM_171830.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.52

Variant links:

Genes affected

KCNMB3 (HGNC:6287): (potassium calcium-activated channel subfamily M regulatory beta subunit 3) MaxiK channels are large conductance, voltage and calcium-sensitive potassium channels which are fundamental to the control of smooth muscle tone and neuronal excitability. MaxiK channels can be formed by 2 subunits: the pore-forming alpha subunit and the modulatory beta subunit. The protein encoded by this gene is an auxiliary beta subunit which may partially inactivate or slightly decrease the activation time of MaxiK alpha subunit currents. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 22. [provided by RefSeq, Jul 2009]

KCNMB3 links:

KCNMB3 (HGNC:):

KCNMB3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018640459).

BP6

Variant 3-179243250-T-C is Benign according to our data. Variant chr3-179243250-T-C is described in ClinVar as [Benign]. Clinvar id is 771137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMB3	NM_171830.2 linkuse as main transcript	c.482A>G	p.Asn161Ser	missense_variant	3/3	ENST00000392685.7	NP_741981.1	Q9NPA1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMB3	ENST00000392685.7 linkuse as main transcript	c.482A>G	p.Asn161Ser	missense_variant	3/3	1	NM_171830.2	ENSP00000376451.2		Q9NPA1-3

Frequencies

GnomAD3 genomes

AF:

0.0519

AC:

7848

AN:

151312

Hom.:

222

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0444

Gnomad AMI

AF:

0.0538

Gnomad AMR

AF:

0.0520

Gnomad ASJ

AF:

0.0868

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.0734

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0573

Gnomad OTH

AF:

0.0715

GnomAD3 exomes

AF:

0.0460

AC:

8048

AN:

174922

Hom.:

256

AF XY:

0.0465

AC XY:

4366

AN XY:

93926

show subpopulations

Gnomad AFR exome

AF:

0.0456

Gnomad AMR exome

AF:

0.0377

Gnomad ASJ exome

AF:

0.0825

Gnomad EAS exome

AF:

0.0000651

Gnomad SAS exome

AF:

0.00899

Gnomad FIN exome

AF:

0.0633

Gnomad NFE exome

AF:

0.0579

Gnomad OTH exome

AF:

0.0524

GnomAD4 exome

AF:

0.0488

AC:

56943

AN:

1166388

Hom.:

1636

Cov.:

AF XY:

0.0481

AC XY:

28400

AN XY:

590910

show subpopulations

Gnomad4 AFR exome

AF:

0.0456

Gnomad4 AMR exome

AF:

0.0383

Gnomad4 ASJ exome

AF:

0.0847

Gnomad4 EAS exome

AF:

0.0000521

Gnomad4 SAS exome

AF:

0.0115

Gnomad4 FIN exome

AF:

0.0601

Gnomad4 NFE exome

AF:

0.0529

Gnomad4 OTH exome

AF:

0.0514

GnomAD4 genome

AF:

0.0519

AC:

7863

AN:

151430

Hom.:

223

Cov.:

AF XY:

0.0517

AC XY:

3822

AN XY:

73990

show subpopulations

Gnomad4 AFR

AF:

0.0447

Gnomad4 AMR

AF:

0.0519

Gnomad4 ASJ

AF:

0.0868

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.0734

Gnomad4 NFE

AF:

0.0574

Gnomad4 OTH

AF:

0.0703

Alfa

AF:

0.0520

Hom.:

Bravo

AF:

0.0520

ESP6500AA

AF:

0.0397

AC:

141

ESP6500EA

AF:

0.0486

AC:

372

ExAC

AF:

0.0443

AC:

5292

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0020

.;.;.;T;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.79

.;T;T;T;T

MetaRNN

Benign

0.0019

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

.;.;.;M;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.1

N;.;N;N;N

REVEL

Benign

0.085

Sift

Benign

0.17

T;.;T;T;T

Sift4G

Uncertain

0.019

.;D;T;T;T

Polyphen

0.57

P;.;P;P;B

Vest4

0.049

MPC

1.3

ClinPred

0.011

GERP RS

2.5

Varity_R

0.054

gMVP

0.27

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