11-65593694-G-A

Position:

chr11-65593694-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033347.2(KCNK7):c.500C>T(p.Ala167Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,607,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KCNK7
NM_033347.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.21

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.120961994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK7	NM_033347.2 linkuse as main transcript	c.500C>T	p.Ala167Val	missense_variant	2/3	ENST00000340313.5	NP_203133.1	Q9Y2U2-1
KCNK7	NM_005714.2 linkuse as main transcript	c.500C>T	p.Ala167Val	missense_variant	2/2		NP_005705.1	Q9Y2U2-3A0A024R5F5
KCNK7	NM_033348.2 linkuse as main transcript	c.500C>T	p.Ala167Val	missense_variant	2/4		NP_203134.1	Q9Y2U2-2A0A024R5B0
KCNK7	NM_033455.2 linkuse as main transcript	c.500C>T	p.Ala167Val	missense_variant	2/3		NP_258416.1	Q9Y2U2-2A0A024R5B0Q3SYI1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KCNK7	ENST00000340313.5 linkuse as main transcript	c.500C>T	p.Ala167Val	missense_variant	2/3	1	NM_033347.2	ENSP00000344820.5	Q9Y2U2-1
KCNK7	ENST00000394216.6 linkuse as main transcript	c.500C>T	p.Ala167Val	missense_variant	2/2	1		ENSP00000377764.2	Q9Y2U2-3
KCNK7	ENST00000342202.8 linkuse as main transcript	c.500C>T	p.Ala167Val	missense_variant	2/3	1		ENSP00000343923.4	Q9Y2U2-2
KCNK7	ENST00000394217.6 linkuse as main transcript	c.500C>T	p.Ala167Val	missense_variant	2/4	1		ENSP00000377765.2	Q9Y2U2-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152234

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000172

AC:

AN:

231952

Hom.:

AF XY:

0.0000234

AC XY:

AN XY:

128088

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000331

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000193

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1455092

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724046

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74378

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.00000833

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2024

The c.500C>T (p.A167V) alteration is located in exon 2 (coding exon 2) of the KCNK7 gene. This alteration results from a C to T substitution at nucleotide position 500, causing the alanine (A) at amino acid position 167 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.29

.;.;.;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.54

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.66

.;T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

M;M;M;M

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.1

N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.055

T;T;T;D

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.10

B;B;B;B

Vest4

0.21

MVP

0.24

MPC

0.025

ClinPred

0.11

GERP RS

3.6

Varity_R

0.056

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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