6-39299546-G-T

Variant names:

• chr6-39299546-G-T
• rs944848721
• NM_031460.4:c.880C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031460.4(KCNK17):​c.880C>A​(p.Pro294Thr) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KCNK17 NM_031460.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.270
• Publications: 0 publications found

Genes affected

KCNK17 (HGNC:14465): (potassium two pore domain channel subfamily K member 17) The protein encoded by this gene belongs to the family of potassium channel proteins containing two pore-forming P domains. This channel is an open rectifier which primarily passes outward current under physiological K+ concentrations. This gene is activated at alkaline pH. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

KCNK17 Gene-Disease associations (from GenCC):

• heart conduction disease

  Inheritance: Unknown Classification: LIMITED Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06696755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK17	NM_031460.4	c.880C>A	p.Pro294Thr	missense_variant	Exon 5 of 5	ENST00000373231.9	NP_113648.2
KCNK17	NM_001135111.2	c.*215C>A		3_prime_UTR_variant	Exon 6 of 6		NP_001128583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK17	ENST00000373231.9	c.880C>A	p.Pro294Thr	missense_variant	Exon 5 of 5	1	NM_031460.4	ENSP00000362328.4
KCNK17	ENST00000453413.2	c.*215C>A		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000401271.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.880C>A (p.P294T) alteration is located in exon 5 (coding exon 5) of the KCNK17 gene. This alteration results from a C to A substitution at nucleotide position 880, causing the proline (P) at amino acid position 294 to be replaced by a threonine (T). 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	0.070
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	2.9
DANN	Benign	0.79
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.27
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.10
Sift	Benign	0.17	T
Sift4G	Benign	0.13	T
Polyphen		0.025	B
Vest4		0.052
MutPred		0.19		Gain of phosphorylation at P294 (P = 0.0205);
MVP		0.32
MPC		0.25
ClinPred		0.090	T
GERP RS		3.7
Varity_R		0.061
gMVP		0.25
Mutation Taster		=92/8	polymorphism

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: rs944848721; hg19: chr6-39267322; COSMIC: COSV100950287; COSMIC: COSV100950287;