Variant rs41273124 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_003740.4(KCNK5):c.1094A>T(p.Lys365Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00261 in 1,614,036 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0027 ( 6 hom. )

Consequence

KCNK5
NM_003740.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.78

Variant links:

Genes affected

KCNK5 (HGNC:6280): (potassium two pore domain channel subfamily K member 5) This gene encodes one of the members of the superfamily of potassium channel proteins containing two pore-forming P domains. The message for this gene is mainly expressed in the cortical distal tubules and collecting ducts of the kidney. The protein is highly sensitive to external pH and this, in combination with its expression pattern, suggests it may play an important role in renal potassium transport. [provided by RefSeq, Jul 2008]

KCNK5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008953959).

BP6

Variant 6-39191296-T-A is Benign according to our data. Variant chr6-39191296-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 3043088.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK5	NM_003740.4 link	c.1094A>T	p.Lys365Ile	missense_variant	Exon 5 of 5	ENST00000359534.4	NP_003731.1	O95279A0A024RD32
KCNK5	XM_005249456.2 link	c.1085A>T	p.Lys362Ile	missense_variant	Exon 5 of 5		XP_005249513.1
KCNK5	XM_006715235.2 link	c.548A>T	p.Lys183Ile	missense_variant	Exon 3 of 3		XP_006715298.1	A0A0B6VPR3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK5	ENST00000359534.4 link	c.1094A>T	p.Lys365Ile	missense_variant	Exon 5 of 5	1	NM_003740.4	ENSP00000352527.3		O95279

Frequencies

GnomAD3 genomes

AF:

0.00176

AC:

268

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00293

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00170

AC:

427

AN:

251280

Hom.:

AF XY:

0.00158

AC XY:

214

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.00297

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.00270

AC:

3952

AN:

1461782

Hom.:

Cov.:

AF XY:

0.00253

AC XY:

1839

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.000188

Gnomad4 NFE exome

AF:

0.00334

Gnomad4 OTH exome

AF:

0.00200

GnomAD4 genome

AF:

0.00175

AC:

267

AN:

152254

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

121

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00291

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00266

Hom.:

Bravo

AF:

0.00197

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00314

AC:

ExAC

AF:

0.00162

AC:

197

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KCNK5-related disorder

Benign:1

Mar 18, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.79

M_CAP

Benign

0.030

MetaRNN

Benign

0.0090

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.6

REVEL

Benign

0.24

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.032

Polyphen

1.0

Vest4

0.34

MVP

0.40

MPC

2.2

ClinPred

0.041

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.54

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