6-39299546-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.270

Publications

0 publications found
Variant links:
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

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ACMG classification

Classification was made for transcript

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
KCNK17NM_031460.4 linkc.880C>A p.Pro294Thr missense_variant Exon 5 of 5 ENST00000373231.9 NP_113648.2 Q96T54-3
KCNK17NM_001135111.2 linkc.*215C>A 3_prime_UTR_variant Exon 6 of 6 NP_001128583.1 Q96T54-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KCNK17ENST00000373231.9 linkc.880C>A p.Pro294Thr missense_variant Exon 5 of 5 1 NM_031460.4 ENSP00000362328.4 Q96T54-3
KCNK17ENST00000453413.2 linkc.*215C>A 3_prime_UTR_variant Exon 6 of 6 5 ENSP00000401271.2 Q96T54-4

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
LINK: link

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

Publications

Other links and lift over

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