6-39299509-C-T

Position:

• chr6-39299509-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_031460.4(KCNK17):​c.917G>A​(p.Gly306Glu) 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KCNK17 NM_031460.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.35

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04722923).
• BP6: Variant 6-39299509-C-T is Benign according to our data. Variant chr6-39299509-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3287683.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK17	NM_031460.4	c.917G>A	p.Gly306Glu	missense_variant	5/5	ENST00000373231.9	NP_113648.2
KCNK17	NM_001135111.2	c.*252G>A		3_prime_UTR_variant	6/6		NP_001128583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK17	ENST00000373231.9	c.917G>A	p.Gly306Glu	missense_variant	5/5	1	NM_031460.4	ENSP00000362328.4
KCNK17	ENST00000453413	c.*252G>A		3_prime_UTR_variant	6/6	5		ENSP00000401271.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.91
DANN	Benign	0.60
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.97	L
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.0050
Sift	Benign	0.15	T
Sift4G	Uncertain	0.015	D
Polyphen		0.0	B
Vest4		0.047
MutPred		0.28		Gain of solvent accessibility (P = 0.0456);
MVP		0.16
MPC		0.28
ClinPred		0.058	T
GERP RS		-3.7
Varity_R		0.043
gMVP		0.16

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

LitVar

Other links and lift over

dbSNP: rs1761912772; hg19: chr6-39267285;