Variant 6-39190997-G-T 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_003740.4(KCNK5):c.1393C>A(p.Pro465Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 1,576,484 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.017 ( 70 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 69 hom. )

Consequence

KCNK5
NM_003740.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.76

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019867122).

BP6

Variant 6-39190997-G-T is Benign according to our data. Variant chr6-39190997-G-T is described in ClinVar as [Benign]. Clinvar id is 1239991.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KCNK5	NM_003740.4 linkuse as main transcript	c.1393C>A	p.Pro465Thr	missense_variant	5/5	ENST00000359534.4
KCNK5	XM_005249456.2 linkuse as main transcript	c.1384C>A	p.Pro462Thr	missense_variant	5/5
KCNK5	XM_006715235.2 linkuse as main transcript	c.847C>A	p.Pro283Thr	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK5	ENST00000359534.4 linkuse as main transcript	c.1393C>A	p.Pro465Thr	missense_variant	5/5	1	NM_003740.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0170

AC:

2584

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0589

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00437

AC:

900

AN:

206138

Hom.:

AF XY:

0.00281

AC XY:

312

AN XY:

111080

show subpopulations

Gnomad AFR exome

AF:

0.0576

Gnomad AMR exome

AF:

0.00295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000252

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000107

Gnomad OTH exome

AF:

0.000802

GnomAD4 exome

AF:

0.00165

AC:

2345

AN:

1424168

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

1005

AN XY:

705432

show subpopulations

Gnomad4 AFR exome

AF:

0.0615

Gnomad4 AMR exome

AF:

0.00336

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000411

Gnomad4 OTH exome

AF:

0.00309

GnomAD4 genome

AF:

0.0170

AC:

2583

AN:

152316

Hom.:

Cov.:

AF XY:

0.0162

AC XY:

1210

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0587

Gnomad4 AMR

AF:

0.00653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00401

Hom.:

Bravo

AF:

0.0191

ESP6500AA

AF:

0.0552

AC:

243

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00507

AC:

615

Asia WGS

AF:

0.00231

AC:

AN:

3476

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

GeneDx

Oct 29, 2020

This variant is associated with the following publications: (PMID: 26220970) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0020

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.3

MutationTaster

Benign

0.51

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.3

REVEL

Benign

0.16

Sift

Benign

0.12

Sift4G

Benign

0.29

Polyphen

0.78

Vest4

0.31

MVP

0.20

MPC

0.77

ClinPred

0.019

GERP RS

5.9

Varity_R

0.064

gMVP

0.22

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