6-39304506-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_031460.4(KCNK17):​c.502G>A​(p.Gly168Ser) 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. 15/21 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: 0.578
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06643522).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCNK17NM_031460.4 linkc.502G>A p.Gly168Ser missense_variant Exon 3 of 5 ENST00000373231.9 NP_113648.2 Q96T54-3
KCNK17NM_001135111.2 linkc.502G>A p.Gly168Ser missense_variant Exon 3 of 6 NP_001128583.1 Q96T54-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KCNK17ENST00000373231.9 linkc.502G>A p.Gly168Ser missense_variant Exon 3 of 5 1 NM_031460.4 ENSP00000362328.4 Q96T54-3
KCNK17ENST00000503878.1 linkn.607G>A non_coding_transcript_exon_variant Exon 3 of 3 1
KCNK17ENST00000453413.2 linkc.502G>A p.Gly168Ser missense_variant Exon 3 of 6 5 ENSP00000401271.2 Q96T54-4

Frequencies

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

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.502G>A (p.G168S) alteration is located in exon 3 (coding exon 3) of the KCNK17 gene. This alteration results from a G to A substitution at nucleotide position 502, causing the glycine (G) at amino acid position 168 to be replaced by a serine (S). 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
0.084
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
14
DANN
Benign
0.92
DEOGEN2
Benign
0.0068
T;.
Eigen
Benign
-0.96
Eigen_PC
Benign
-0.86
FATHMM_MKL
Benign
0.076
N
LIST_S2
Benign
0.62
T;T
M_CAP
Benign
0.0037
T
MetaRNN
Benign
0.066
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.61
N;N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.38
N;N
REVEL
Benign
0.025
Sift
Benign
0.60
T;T
Sift4G
Benign
0.72
T;T
Polyphen
0.0020
B;.
Vest4
0.24
MutPred
0.37
Gain of glycosylation at G168 (P = 0.0169);Gain of glycosylation at G168 (P = 0.0169);
MVP
0.34
MPC
0.23
ClinPred
0.031
T
GERP RS
0.98
Varity_R
0.037
gMVP
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-39272282; API