Variant 14-90184170-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_022054.4(KCNK13):c.394C>T(p.Leu132Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00648 in 1,614,220 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0066 ( 41 hom. )

Consequence

KCNK13
NM_022054.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.13

Variant links:

Genes affected

KCNK13 (HGNC:6275): (potassium two pore domain channel subfamily K member 13) Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a potassium channel containing two pore-forming domains. This protein is an open channel that can be stimulated by arachidonic acid and inhibited by the anesthetic halothane. [provided by RefSeq, Jul 2013]

KCNK13 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=0.018620014).

BP6

Variant 14-90184170-C-T is Benign according to our data. Variant chr14-90184170-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2644447.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNK13	NM_022054.4 linkuse as main transcript	c.394C>T	p.Leu132Phe	missense_variant	2/2	ENST00000282146.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK13	ENST00000282146.5 linkuse as main transcript	c.394C>T	p.Leu132Phe	missense_variant	2/2	1	NM_022054.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00556

AC:

847

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00817

Gnomad OTH

AF:

0.00907

GnomAD3 exomes

AF:

0.00406

AC:

1022

AN:

251424

Hom.:

AF XY:

0.00401

AC XY:

545

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00552

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000832

Gnomad NFE exome

AF:

0.00664

Gnomad OTH exome

AF:

0.00636

GnomAD4 exome

AF:

0.00658

AC:

9612

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00637

AC XY:

4631

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00570

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00114

Gnomad4 NFE exome

AF:

0.00797

Gnomad4 OTH exome

AF:

0.00624

GnomAD4 genome

AF:

0.00555

AC:

846

AN:

152344

Hom.:

Cov.:

AF XY:

0.00546

AC XY:

407

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.0118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.00816

Gnomad4 OTH

AF:

0.00898

Alfa

AF:

0.00691

Hom.:

Bravo

AF:

0.00552

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00849

AC:

ExAC

AF:

0.00378

AC:

459

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00889

EpiControl

AF:

0.00747

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

KCNK13: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.010

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.32

Sift

Benign

0.32

Sift4G

Benign

0.30

Polyphen

0.74

Vest4

0.88

MVP

0.68

MPC

0.65

ClinPred

0.055

GERP RS

5.3

Varity_R

0.14

gMVP

0.88

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