Variant 3-179243237-G-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.495C>G(p.Asn165Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,338,854 control chromosomes in the GnomAD database, including 805 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N165S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.015 ( 85 hom., cov: 30)

Exomes 𝑓: 0.012 ( 720 hom. )

Consequence

KCNMB3
NM_171830.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.49

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:

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=0.0016209185).

BP6

Variant 3-179243237-G-C is Benign according to our data. Variant chr3-179243237-G-C is described in ClinVar as [Benign]. Clinvar id is 773453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMB3	NM_171830.2 link	c.495C>G	p.Asn165Lys	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 link	c.495C>G	p.Asn165Lys	missense_variant	3/3	1	NM_171830.2	ENSP00000376451.2		Q9NPA1-3

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2327

AN:

151144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0326

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.00264

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00309

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.000191

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00399

Gnomad OTH

AF:

0.00722

GnomAD3 exomes

AF:

0.0169

AC:

3125

AN:

184658

Hom.:

170

AF XY:

0.0195

AC XY:

1934

AN XY:

99434

show subpopulations

Gnomad AFR exome

AF:

0.0313

Gnomad AMR exome

AF:

0.00260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00159

Gnomad SAS exome

AF:

0.129

Gnomad FIN exome

AF:

0.0000560

Gnomad NFE exome

AF:

0.00373

Gnomad OTH exome

AF:

0.0112

GnomAD4 exome

AF:

0.0123

AC:

14650

AN:

1187594

Hom.:

720

Cov.:

AF XY:

0.0156

AC XY:

9413

AN XY:

601870

show subpopulations

Gnomad4 AFR exome

AF:

0.0363

Gnomad4 AMR exome

AF:

0.00226

Gnomad4 ASJ exome

AF:

0.0000893

Gnomad4 EAS exome

AF:

0.00356

Gnomad4 SAS exome

AF:

0.122

Gnomad4 FIN exome

AF:

0.000172

Gnomad4 NFE exome

AF:

0.00420

Gnomad4 OTH exome

AF:

0.0118

GnomAD4 genome

AF:

0.0154

AC:

2329

AN:

151260

Hom.:

Cov.:

AF XY:

0.0171

AC XY:

1261

AN XY:

73846

show subpopulations

Gnomad4 AFR

AF:

0.0326

Gnomad4 AMR

AF:

0.00264

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00309

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.000191

Gnomad4 NFE

AF:

0.00400

Gnomad4 OTH

AF:

0.00715

Alfa

AF:

0.00821

Hom.:

Bravo

AF:

0.0133

ESP6500AA

AF:

0.0218

AC:

ESP6500EA

AF:

0.00348

AC:

ExAC

AF:

0.0198

AC:

2372

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	Jul 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.00071

.;.;.;T;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.64

.;T;T;T;T

MetaRNN

Benign

0.0016

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.3

.;.;.;M;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.3

N;.;N;N;N

REVEL

Benign

0.084

Sift

Benign

0.077

T;.;T;T;T

Sift4G

Uncertain

0.051

.;T;T;T;T

Polyphen

0.029

B;.;B;B;B

Vest4

0.082

MutPred

0.39

.;.;.;Gain of ubiquitination at N169 (P = 0.0258);.;

MPC

1.8

ClinPred

0.0071

GERP RS

4.2

Varity_R

0.10

gMVP

0.42

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