3-179242932-C-T

Position:

• chr3-179242932-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_171830.2(KCNMB3):​c.800G>A​(p.Arg267Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KCNMB3 NM_171830.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.214

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062965244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMB3	NM_171830.2	c.800G>A	p.Arg267Lys	missense_variant	3/3	ENST00000392685.7	NP_741981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMB3	ENST00000392685.7	c.800G>A	p.Arg267Lys	missense_variant	3/3	1	NM_171830.2	ENSP00000376451.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 18, 2021

The c.800G>A (p.R267K) alteration is located in exon 3 (coding exon 3) of the KCNMB3 gene. This alteration results from a G to A substitution at nucleotide position 800, causing the arginine (R) at amino acid position 267 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.7
DANN	Benign	0.90
DEOGEN2	Benign	0.00079	.;.;T;.
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.39	.;T;T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.063	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	.;.;L;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.14	N;N;N;N
REVEL	Benign	0.019
Sift	Benign	0.63	T;T;T;T
Sift4G	Pathogenic	0.0	.;D;D;D
Polyphen		0.0010	B;B;B;B
Vest4		0.067
MutPred		0.34		.;.;Gain of methylation at R271 (P = 0.0206);.;
MVP		0.30
MPC		1.2
ClinPred		0.14	T
GERP RS		1.4
Varity_R		0.044
gMVP		0.059

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-178960720;