Variant 6-39191171-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003740.4(KCNK5):c.1219G>A(p.Ala407Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00335 in 1,614,206 control chromosomes in the GnomAD database, including 16 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 (★).

Frequency

Genomes: 𝑓 0.0033 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0034 ( 15 hom. )

Consequence

KCNK5
NM_003740.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.46

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027202666).

BP6

Variant 6-39191171-C-T is Benign according to our data. Variant chr6-39191171-C-T is described in ClinVar as [Benign]. Clinvar id is 790348.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KCNK5	NM_003740.4 linkuse as main transcript	c.1219G>A	p.Ala407Thr	missense_variant	5/5	ENST00000359534.4
KCNK5	XM_005249456.2 linkuse as main transcript	c.1210G>A	p.Ala404Thr	missense_variant	5/5
KCNK5	XM_006715235.2 linkuse as main transcript	c.673G>A	p.Ala225Thr	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK5	ENST00000359534.4 linkuse as main transcript	c.1219G>A	p.Ala407Thr	missense_variant	5/5	1	NM_003740.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00328

AC:

500

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0183

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00375

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00377

AC:

948

AN:

251414

Hom.:

AF XY:

0.00390

AC XY:

530

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00157

Gnomad FIN exome

AF:

0.0187

Gnomad NFE exome

AF:

0.00380

Gnomad OTH exome

AF:

0.00407

GnomAD4 exome

AF:

0.00336

AC:

4908

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00328

AC XY:

2383

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000760

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00146

Gnomad4 FIN exome

AF:

0.0175

Gnomad4 NFE exome

AF:

0.00327

Gnomad4 OTH exome

AF:

0.00260

GnomAD4 genome

AF:

0.00328

AC:

500

AN:

152330

Hom.:

Cov.:

AF XY:

0.00399

AC XY:

297

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.0183

Gnomad4 NFE

AF:

0.00375

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00327

Hom.:

Bravo

AF:

0.00208

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00349

AC:

ExAC

AF:

0.00362

AC:

440

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00409

EpiControl

AF:

0.00338

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

Nov 02, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.70

MetaRNN

Benign

0.0027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.86

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.57

REVEL

Benign

0.062

Sift

Benign

0.067

Sift4G

Benign

0.54

Polyphen

0.0040

Vest4

0.021

MVP

0.19

MPC

0.65

ClinPred

0.013

GERP RS

2.2

Varity_R

0.037

gMVP

0.17

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