Genetic Variant KCNK7:p.Val203Ile (chr11-65593587-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_033347.2(KCNK7):c.607G>A(p.Val203Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000834 in 1,606,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

KCNK7
NM_033347.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.73

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063397884).

BP6

Variant 11-65593587-C-T is Benign according to our data. Variant chr11-65593587-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3532594.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033347.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCNK7	NM_033347.2	MANE Select	c.607G>A	p.Val203Ile	missense	Exon 2 of 3	NP_203133.1	Q9Y2U2-1
KCNK7	NM_005714.2		c.607G>A	p.Val203Ile	missense	Exon 2 of 2	NP_005705.1	Q9Y2U2-3
KCNK7	NM_033348.2		c.607G>A	p.Val203Ile	missense	Exon 2 of 4	NP_203134.1	Q9Y2U2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCNK7	ENST00000340313.5	TSL:1 MANE Select	c.607G>A	p.Val203Ile	missense	Exon 2 of 3	ENSP00000344820.5	Q9Y2U2-1
KCNK7	ENST00000394216.6	TSL:1	c.607G>A	p.Val203Ile	missense	Exon 2 of 2	ENSP00000377764.2	Q9Y2U2-3
KCNK7	ENST00000342202.8	TSL:1	c.607G>A	p.Val203Ile	missense	Exon 2 of 3	ENSP00000343923.4	Q9Y2U2-2

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000127

AC:

AN:

235830

AF XY:

0.0000851

show subpopulations

Gnomad AFR exome

AF:

0.000475

Gnomad AMR exome

AF:

0.000321

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

Gnomad FIN exome

AF:

0.0000612

Gnomad NFE exome

AF:

0.0000657

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.0000681

AC:

AN:

1454262

Hom.:

Cov.:

AF XY:

0.0000663

AC XY:

AN XY:

723828

show subpopulations

African (AFR)

AF:

0.000627

AC:

AN:

33480

American (AMR)

AF:

0.000358

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.000151

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46034

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000333

AC:

AN:

1111882

Other (OTH)

AF:

0.000149

AC:

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000230

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.000625

AC:

AN:

41578

American (AMR)

AF:

0.000131

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.000272

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000907

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.015

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.12

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.48

M_CAP

Benign

0.0018

MetaRNN

Benign

0.0063

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.85

PhyloP100

-1.7

PrimateAI

Benign

0.27

PROVEAN

Benign

0.81

REVEL

Benign

0.018

Sift

Benign

0.79

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.064

MVP

0.19

MPC

0.020

ClinPred

0.0083

GERP RS

-11

PromoterAI

0.034

Neutral

(source)

Varity_R

0.020

gMVP

0.16

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over