chr11-65593842-C-T

Position:

chr11-65593842-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_033347.2(KCNK7):c.352G>A(p.Gly118Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000232 in 1,549,988 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 Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

KCNK7
NM_033347.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.05

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.983

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK7	NM_033347.2 linkuse as main transcript	c.352G>A	p.Gly118Arg	missense_variant	2/3	ENST00000340313.5	NP_203133.1	Q9Y2U2-1
KCNK7	NM_005714.2 linkuse as main transcript	c.352G>A	p.Gly118Arg	missense_variant	2/2		NP_005705.1	Q9Y2U2-3A0A024R5F5
KCNK7	NM_033348.2 linkuse as main transcript	c.352G>A	p.Gly118Arg	missense_variant	2/4		NP_203134.1	Q9Y2U2-2A0A024R5B0
KCNK7	NM_033455.2 linkuse as main transcript	c.352G>A	p.Gly118Arg	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.352G>A	p.Gly118Arg	missense_variant	2/3	1	NM_033347.2	ENSP00000344820.5	Q9Y2U2-1
KCNK7	ENST00000394216.6 linkuse as main transcript	c.352G>A	p.Gly118Arg	missense_variant	2/2	1		ENSP00000377764.2	Q9Y2U2-3
KCNK7	ENST00000342202.8 linkuse as main transcript	c.352G>A	p.Gly118Arg	missense_variant	2/3	1		ENSP00000343923.4	Q9Y2U2-2
KCNK7	ENST00000394217.6 linkuse as main transcript	c.352G>A	p.Gly118Arg	missense_variant	2/4	1		ENSP00000377765.2	Q9Y2U2-2

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000568

AC:

AN:

193668

Hom.:

AF XY:

0.0000756

AC XY:

AN XY:

105812

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000389

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:

0.0000113

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000222

AC:

AN:

1397770

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

688264

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000423

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:

0.0000148

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.0000499

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

Dec 12, 2023

The c.352G>A (p.G118R) alteration is located in exon 2 (coding exon 2) of the KCNK7 gene. This alteration results from a G to A substitution at nucleotide position 352, causing the glycine (G) at amino acid position 118 to be replaced by an arginine (R). 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

Pathogenic

0.60

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Pathogenic

0.31

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.90

.;.;.;D

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.74

.;T;T;T

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.98

D;D;D;D

MetaSVM

Uncertain

-0.029

MutationAssessor

Pathogenic

4.0

H;H;H;H

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-7.5

D;D;D;D

REVEL

Pathogenic

0.67

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.96

MutPred

0.94

Loss of ubiquitination at K119 (P = 0.0561);Loss of ubiquitination at K119 (P = 0.0561);Loss of ubiquitination at K119 (P = 0.0561);Loss of ubiquitination at K119 (P = 0.0561);

MVP

0.70

MPC

0.18

ClinPred

1.0

GERP RS

5.5

Varity_R

0.79

gMVP

0.93

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