Variant 11-65593646-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_033347.2(KCNK7):c.548T>C(p.Val183Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000374 in 1,604,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

KCNK7
NM_033347.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.34

Variant links:

Genes affected

KCNK7 (HGNC:6282): (potassium two pore domain channel subfamily K member 7) This gene encodes a member of the superfamily of potassium channel proteins containing two pore-forming P domains. The product of this gene has not been shown to be a functional channel; however, it may require other non-pore-forming proteins for activity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

KCNK7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26751497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KCNK7	NM_033347.2 linkuse as main transcript	c.548T>C	p.Val183Ala	missense_variant	2/3	ENST00000340313.5
KCNK7	NM_005714.2 linkuse as main transcript	c.548T>C	p.Val183Ala	missense_variant	2/2
KCNK7	NM_033348.2 linkuse as main transcript	c.548T>C	p.Val183Ala	missense_variant	2/4
KCNK7	NM_033455.2 linkuse as main transcript	c.548T>C	p.Val183Ala	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK7	ENST00000340313.5 linkuse as main transcript	c.548T>C	p.Val183Ala	missense_variant	2/3	1	NM_033347.2	P1	Q9Y2U2-1
KCNK7	ENST00000394216.6 linkuse as main transcript	c.548T>C	p.Val183Ala	missense_variant	2/2	1			Q9Y2U2-3
KCNK7	ENST00000342202.8 linkuse as main transcript	c.548T>C	p.Val183Ala	missense_variant	2/3	1			Q9Y2U2-2
KCNK7	ENST00000394217.6 linkuse as main transcript	c.548T>C	p.Val183Ala	missense_variant	2/4	1			Q9Y2U2-2

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000174

AC:

AN:

230342

Hom.:

AF XY:

0.0000315

AC XY:

AN XY:

127088

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000387

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000379

AC:

AN:

1452268

Hom.:

Cov.:

AF XY:

0.0000401

AC XY:

AN XY:

722722

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000486

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000234

AC:

ExAC

AF:

0.0000415

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.97

M_CAP

Benign

0.030

MetaRNN

Benign

0.27

T;T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.6

M;M;M;M

MutationTaster

Benign

0.52

N;N;N;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.0

N;N;N;N

REVEL

Benign

0.19

Sift

Uncertain

0.015

D;D;D;D

Sift4G

Uncertain

0.041

D;D;D;T

Polyphen

0.57

P;P;P;P

Vest4

0.43

MVP

0.32

MPC

0.048

ClinPred

0.47

GERP RS

4.4

Varity_R

0.13

gMVP

0.57

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over