3-179242978-CTT-CTTT

Variant names:

• chr3-179242978-C-CT
• rs143962239
• NM_171830.2:c.753dupA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_171830.2(KCNMB3):​c.753dupA​(p.Val252SerfsTer31) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 28)
• Consequence: KCNMB3 NM_171830.2 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.485
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_171830.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB3	NM_171830.2	MANE Select	c.753dupA	p.Val252SerfsTer31	frameshift	Exon 3 of 3	NP_741981.1
	KCNMB3	NM_014407.3		c.765dupA	p.Val256SerfsTer31	frameshift	Exon 4 of 4	NP_055222.3
	KCNMB3	NM_171828.3		c.759dupA	p.Val254SerfsTer31	frameshift	Exon 4 of 4	NP_741979.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB3	ENST00000392685.7	TSL:1 MANE Select	c.753dupA	p.Val252SerfsTer31	frameshift	Exon 3 of 3	ENSP00000376451.2
	KCNMB3	ENST00000314235.9	TSL:1	c.765dupA	p.Val256SerfsTer31	frameshift	Exon 4 of 4	ENSP00000319370.5
	KCNMB3	ENST00000485523.5	TSL:1	c.699dupA	p.Val234SerfsTer31	frameshift	Exon 4 of 4	ENSP00000418536.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 28

Alfa AF: 0.00 Hom.: 142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.48

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

Other links and lift over

dbSNP: rs143962239; hg19: chr3-178960766;