Variant 6-39310983-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_031460.4(KCNK17):c.262G>A(p.Gly88Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000294 in 1,597,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

KCNK17
NM_031460.4 missense

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.21

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.986

PP5

Variant 6-39310983-C-T is Pathogenic according to our data. Variant chr6-39310983-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 132903.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK17	NM_031460.4 linkuse as main transcript	c.262G>A	p.Gly88Arg	missense_variant	2/5	ENST00000373231.9	NP_113648.2
KCNK17	NM_001135111.2 linkuse as main transcript	c.262G>A	p.Gly88Arg	missense_variant	2/6		NP_001128583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK17	ENST00000373231.9 linkuse as main transcript	c.262G>A	p.Gly88Arg	missense_variant	2/5	1	NM_031460.4	ENSP00000362328	P1	Q96T54-3
KCNK17	ENST00000503878.1 linkuse as main transcript	n.367G>A		non_coding_transcript_exon_variant	2/3	1
KCNK17	ENST00000453413.2 linkuse as main transcript	c.262G>A	p.Gly88Arg	missense_variant	2/6	5		ENSP00000401271		Q96T54-4

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

151098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000443

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

249594

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134976

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000584

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000304

AC:

AN:

1446040

Hom.:

Cov.:

AF XY:

0.0000195

AC XY:

AN XY:

717622

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000454

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000363

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000199

AC:

AN:

151098

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73758

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000443

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000283

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Likely pathogenic, no assertion criteria provided

literature only

Institute for Genetics of Heart Diseases, University Hospital Muenster

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Uncertain

0.090

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.27

T;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.55

T;T

M_CAP

Pathogenic

0.36

MetaRNN

Pathogenic

0.99

D;D

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.8

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-7.6

D;D

REVEL

Pathogenic

0.74

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;.

Vest4

0.96

MutPred

0.62

Gain of methylation at G88 (P = 0.0303);Gain of methylation at G88 (P = 0.0303);

MVP

0.62

MPC

0.91

ClinPred

0.97

GERP RS

5.4

Varity_R

0.60

gMVP

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over