6-39304506-C-T

Variant names:

• chr6-39304506-C-T
• NM_031460.4:c.502G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.578

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]

ACMG classification

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
KCNK17	NM_031460.4	c.502G>A	p.Gly168Ser	missense_variant	Exon 3 of 5	ENST00000373231.9	NP_113648.2
KCNK17	NM_001135111.2	c.502G>A	p.Gly168Ser	missense_variant	Exon 3 of 6		NP_001128583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK17	ENST00000373231.9	c.502G>A	p.Gly168Ser	missense_variant	Exon 3 of 5	1	NM_031460.4	ENSP00000362328.4
KCNK17	ENST00000503878.1	n.607G>A		non_coding_transcript_exon_variant	Exon 3 of 3	1
KCNK17	ENST00000453413.2	c.502G>A	p.Gly168Ser	missense_variant	Exon 3 of 6	5		ENSP00000401271.2

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

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;