6-39303993-T-G

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>C​(p.Thr218Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T218A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

KCNK17
NM_031460.4 missense

Scores

8
9
2

Clinical Significance

Not reported in ClinVar

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, 0.917

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCNK17NM_031460.4 linkc.652A>C p.Thr218Pro missense_variant Exon 4 of 5 ENST00000373231.9 NP_113648.2 Q96T54-3
KCNK17NM_001135111.2 linkc.652A>C p.Thr218Pro 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>C p.Thr218Pro missense_variant Exon 4 of 5 1 NM_031460.4 ENSP00000362328.4 Q96T54-3
KCNK17ENST00000503878.1 linkn.1120A>C non_coding_transcript_exon_variant Exon 3 of 3 1
KCNK17ENST00000453413.2 linkc.652A>C p.Thr218Pro missense_variant Exon 4 of 6 5 ENSP00000401271.2 Q96T54-4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.82
BayesDel_addAF
Pathogenic
0.34
D
BayesDel_noAF
Pathogenic
0.25
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.81
D;.
Eigen
Pathogenic
0.79
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.050
D
MetaRNN
Pathogenic
0.92
D;D
MetaSVM
Uncertain
0.45
D
MutationAssessor
Pathogenic
4.1
H;H
PhyloP100
5.5
PrimateAI
Uncertain
0.50
T
PROVEAN
Pathogenic
-5.5
D;D
REVEL
Uncertain
0.61
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0020
D;D
Polyphen
1.0
D;.
Vest4
0.78
MutPred
0.81
Gain of glycosylation at S220 (P = 0.0944);Gain of glycosylation at S220 (P = 0.0944);
MVP
0.85
MPC
0.95
ClinPred
1.0
D
GERP RS
4.2
Varity_R
0.91
gMVP
0.93
Mutation Taster
=79/21
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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