Variant chr6-39310980-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_031460.4(KCNK17):c.265G>A(p.Ala89Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000987 in 1,606,334 control chromosomes in the GnomAD database, including 6 homozygotes. 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: 𝑓 0.00086 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0010 ( 6 hom. )

Consequence

KCNK17
NM_031460.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.06

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00647521).

BP6

Variant 6-39310980-C-T is Benign according to our data. Variant chr6-39310980-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656532.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK17	NM_031460.4 linkuse as main transcript	c.265G>A	p.Ala89Thr	missense_variant	2/5	ENST00000373231.9	NP_113648.2
KCNK17	NM_001135111.2 linkuse as main transcript	c.265G>A	p.Ala89Thr	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.265G>A	p.Ala89Thr	missense_variant	2/5	1	NM_031460.4	ENSP00000362328	P1	Q96T54-3
KCNK17	ENST00000503878.1 linkuse as main transcript	n.370G>A		non_coding_transcript_exon_variant	2/3	1
KCNK17	ENST00000453413.2 linkuse as main transcript	c.265G>A	p.Ala89Thr	missense_variant	2/6	5		ENSP00000401271		Q96T54-4

Frequencies

GnomAD3 genomes

AF:

0.000849

AC:

129

AN:

151870

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00272

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00115

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00100

AC:

251

AN:

249922

Hom.:

AF XY:

0.00122

AC XY:

165

AN XY:

135144

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000350

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00273

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00123

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.00100

AC:

1456

AN:

1454346

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

815

AN XY:

722060

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.000496

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00342

Gnomad4 FIN exome

AF:

0.000113

Gnomad4 NFE exome

AF:

0.000947

Gnomad4 OTH exome

AF:

0.000800

GnomAD4 genome

AF:

0.000855

AC:

130

AN:

151988

Hom.:

Cov.:

AF XY:

0.000835

AC XY:

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00151

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00272

Gnomad4 FIN

AF:

0.000284

Gnomad4 NFE

AF:

0.00116

Gnomad4 OTH

AF:

0.00238

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.000888

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00112

AC:

136

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00175

EpiControl

AF:

0.00172

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

KCNK17: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.9

DANN

Benign

0.96

DEOGEN2

Benign

0.010

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.0065

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.15

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.13

N;N

REVEL

Benign

0.058

Sift

Benign

0.25

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.0090

B;.

Vest4

0.077

MVP

0.25

MPC

0.21

ClinPred

0.0031

GERP RS

-1.4

Varity_R

0.043

gMVP

0.37

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

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