6-39303993-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_031460.4(KCNK17):​c.652A>G​(p.Thr218Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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

4
13
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.53

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: Uncertain_significance. The variant received 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.886

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCNK17NM_031460.4 linkc.652A>G p.Thr218Ala missense_variant Exon 4 of 5 ENST00000373231.9 NP_113648.2 Q96T54-3
KCNK17NM_001135111.2 linkc.652A>G p.Thr218Ala missense_variant Exon 4 of 6 NP_001128583.1 Q96T54-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KCNK17ENST00000373231.9 linkc.652A>G p.Thr218Ala missense_variant Exon 4 of 5 1 NM_031460.4 ENSP00000362328.4 Q96T54-3
KCNK17ENST00000503878.1 linkn.1120A>G non_coding_transcript_exon_variant Exon 3 of 3 1
KCNK17ENST00000453413.2 linkc.652A>G p.Thr218Ala missense_variant Exon 4 of 6 5 ENSP00000401271.2 Q96T54-4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 01, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.652A>G (p.T218A) alteration is located in exon 4 (coding exon 4) of the KCNK17 gene. This alteration results from a A to G substitution at nucleotide position 652, causing the threonine (T) at amino acid position 218 to be replaced by an alanine (A). 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
Pathogenic
0.75
BayesDel_addAF
Pathogenic
0.16
D
BayesDel_noAF
Uncertain
-0.010
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.60
D;.
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Benign
0.024
T
MetaRNN
Pathogenic
0.89
D;D
MetaSVM
Uncertain
-0.15
T
MutationAssessor
Uncertain
2.4
M;M
PhyloP100
5.5
PrimateAI
Uncertain
0.51
T
PROVEAN
Pathogenic
-4.5
D;D
REVEL
Uncertain
0.47
Sift
Uncertain
0.0040
D;D
Sift4G
Uncertain
0.0040
D;D
Polyphen
1.0
D;.
Vest4
0.86
MutPred
0.77
Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP
0.83
MPC
0.81
ClinPred
0.99
D
GERP RS
4.2
Varity_R
0.37
gMVP
0.75
Mutation Taster
=82/18
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: rs943061480; hg19: chr6-39271769; API