Variant chr11-65593838-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_033347.2(KCNK7):c.356A>G(p.Lys119Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00302 in 1,553,484 control chromosomes in the GnomAD database, including 143 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0077 ( 27 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 116 hom. )

Consequence

KCNK7
NM_033347.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.14

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031587481).

BP6

Variant 11-65593838-T-C is Benign according to our data. Variant chr11-65593838-T-C is described in ClinVar as [Benign]. Clinvar id is 768454.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK7	NM_033347.2 linkuse as main transcript	c.356A>G	p.Lys119Arg	missense_variant	2/3	ENST00000340313.5	NP_203133.1	Q9Y2U2-1
KCNK7	NM_005714.2 linkuse as main transcript	c.356A>G	p.Lys119Arg	missense_variant	2/2		NP_005705.1	Q9Y2U2-3A0A024R5F5
KCNK7	NM_033348.2 linkuse as main transcript	c.356A>G	p.Lys119Arg	missense_variant	2/4		NP_203134.1	Q9Y2U2-2A0A024R5B0
KCNK7	NM_033455.2 linkuse as main transcript	c.356A>G	p.Lys119Arg	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.356A>G	p.Lys119Arg	missense_variant	2/3	1	NM_033347.2	ENSP00000344820.5	Q9Y2U2-1
KCNK7	ENST00000394216.6 linkuse as main transcript	c.356A>G	p.Lys119Arg	missense_variant	2/2	1		ENSP00000377764.2	Q9Y2U2-3
KCNK7	ENST00000342202.8 linkuse as main transcript	c.356A>G	p.Lys119Arg	missense_variant	2/3	1		ENSP00000343923.4	Q9Y2U2-2
KCNK7	ENST00000394217.6 linkuse as main transcript	c.356A>G	p.Lys119Arg	missense_variant	2/4	1		ENSP00000377765.2	Q9Y2U2-2

Frequencies

GnomAD3 genomes

AF:

0.00769

AC:

1171

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0161

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0823

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00884

AC:

1735

AN:

196318

Hom.:

AF XY:

0.00777

AC XY:

836

AN XY:

107592

show subpopulations

Gnomad AFR exome

AF:

0.0167

Gnomad AMR exome

AF:

0.000627

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0858

Gnomad SAS exome

AF:

0.00236

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00608

GnomAD4 exome

AF:

0.00251

AC:

3511

AN:

1401174

Hom.:

116

Cov.:

AF XY:

0.00242

AC XY:

1669

AN XY:

690578

show subpopulations

Gnomad4 AFR exome

AF:

0.0166

Gnomad4 AMR exome

AF:

0.000815

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0584

Gnomad4 SAS exome

AF:

0.00227

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000546

Gnomad4 OTH exome

AF:

0.00777

GnomAD4 genome

AF:

0.00771

AC:

1175

AN:

152310

Hom.:

Cov.:

AF XY:

0.00826

AC XY:

615

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0161

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0827

Gnomad4 SAS

AF:

0.00539

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00403

Hom.:

Bravo

AF:

0.00941

ESP6500AA

AF:

0.0128

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00751

AC:

904

Asia WGS

AF:

0.0390

AC:

136

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 11, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.63

.;.;.;D

Eigen

Benign

-0.11

Eigen_PC

Benign

0.0083

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.64

.;T;T;T

MetaRNN

Benign

0.0032

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;L;L;L

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.2

N;N;N;N

REVEL

Benign

0.098

Sift

Benign

0.036

D;D;D;D

Sift4G

Benign

0.077

T;T;T;T

Polyphen

0.60

P;P;P;P

Vest4

0.41

MVP

0.47

MPC

0.030

ClinPred

0.14

GERP RS

4.3

Varity_R

0.45

gMVP

0.60

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