dbSNP rs1761912772: KCNK17:p.Gly306Val (chr6-39299509-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_031460.4(KCNK17):c.917G>T(p.Gly306Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign 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. G306E) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KCNK17
NM_031460.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.35

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

KCNK17 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05737886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK17	NM_031460.4 link	c.917G>T	p.Gly306Val	missense_variant	Exon 5 of 5	ENST00000373231.9	NP_113648.2	Q96T54-3
KCNK17	NM_001135111.2 link	c.*252G>T		3_prime_UTR_variant	Exon 6 of 6		NP_001128583.1	Q96T54-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK17	ENST00000373231.9 link	c.917G>T	p.Gly306Val	missense_variant	Exon 5 of 5	1	NM_031460.4	ENSP00000362328.4		Q96T54-3
KCNK17	ENST00000453413.2 link	c.*252G>T		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000401271.2		Q96T54-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112012

Other (OTH)

AF:

0.0000331

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

5.1

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.029

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.50

M_CAP

Benign

0.0055

MetaRNN

Benign

0.057

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.97

PhyloP100

-1.4

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.92

REVEL

Benign

0.0040

Sift

Uncertain

0.011

Sift4G

Uncertain

0.020

Polyphen

0.019

Vest4

0.11

MutPred

0.36

Gain of stability (P = 0.047);

MVP

0.17

MPC

0.31

ClinPred

0.071

GERP RS

-3.7

Varity_R

0.053

gMVP

0.23

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs1761912772

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over