3-179250844-AGC-GGT

Variant names:

• chr3-179250844-AGC-GGT
• NM_171830.2:c.145_147delGCTinsACC
• KCNMB3 p.Ala49Thr

Variant summary

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

The NM_171830.2(KCNMB3):​c.145_147delGCTinsACC​(p.Ala49Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNMB3 NM_171830.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.18
• Publications: 0 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 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB3	NM_171830.2	MANE Select	c.145_147delGCTinsACC	p.Ala49Thr	missense	N/A	NP_741981.1	Q9NPA1-3
	KCNMB3	NM_014407.3		c.157_159delGCTinsACC	p.Ala53Thr	missense	N/A	NP_055222.3	Q9NPA1-1
	KCNMB3	NM_171828.3		c.151_153delGCTinsACC	p.Ala51Thr	missense	N/A	NP_741979.1	Q9NPA1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB3	ENST00000392685.7	TSL:1 MANE Select	c.145_147delGCTinsACC	p.Ala49Thr	missense	N/A	ENSP00000376451.2	Q9NPA1-3
	KCNMB3	ENST00000314235.9	TSL:1	c.157_159delGCTinsACC	p.Ala53Thr	missense	N/A	ENSP00000319370.5	Q9NPA1-1
	KCNMB3	ENST00000485523.5	TSL:1	c.91_93delGCTinsACC	p.Ala31Thr	missense	N/A	ENSP00000418536.1	Q9NPA1-4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-178968632;