Variant 6-39316287-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_001135106.2(KCNK16):c.817G>A(p.Val273Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00574 in 1,597,838 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 5 hom., cov: 34)

Exomes 𝑓: 0.0059 ( 28 hom. )

Consequence

KCNK16
NM_001135106.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.314

Variant links:

Genes affected

KCNK16 (HGNC:14464): (potassium two pore domain channel subfamily K member 16) The protein encoded by this gene belongs to the family of potassium channel proteins containing two pore-forming P domains. This channel is an open rectifier which primarily passes outward current under physiological K+ concentrations. This gene is expressed predominantly in the pancreas and is activated at alkaline pH. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Sep 2008]

KCNK16 links:

LOC105375047 (HGNC:):

LOC105375047 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051452518).

BP6

Variant 6-39316287-C-T is Benign according to our data. Variant chr6-39316287-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656535.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK16	NM_001135106.2 linkuse as main transcript	c.817G>A	p.Val273Ile	missense_variant	5/5	ENST00000437525.3	NP_001128578.1	Q96T55-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK16	ENST00000437525.3 linkuse as main transcript	c.817G>A	p.Val273Ile	missense_variant	5/5	1	NM_001135106.2	ENSP00000415375.2		Q96T55-3

Frequencies

GnomAD3 genomes

AF:

0.00411

AC:

625

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0119

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00565

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00357

AC:

776

AN:

217146

Hom.:

AF XY:

0.00359

AC XY:

423

AN XY:

117776

show subpopulations

Gnomad AFR exome

AF:

0.000795

Gnomad AMR exome

AF:

0.00244

Gnomad ASJ exome

AF:

0.000108

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00122

Gnomad FIN exome

AF:

0.00825

Gnomad NFE exome

AF:

0.00498

Gnomad OTH exome

AF:

0.00409

GnomAD4 exome

AF:

0.00591

AC:

8538

AN:

1445556

Hom.:

Cov.:

AF XY:

0.00573

AC XY:

4108

AN XY:

717342

show subpopulations

Gnomad4 AFR exome

AF:

0.000841

Gnomad4 AMR exome

AF:

0.00270

Gnomad4 ASJ exome

AF:

0.0000390

Gnomad4 EAS exome

AF:

0.000128

Gnomad4 SAS exome

AF:

0.00124

Gnomad4 FIN exome

AF:

0.00769

Gnomad4 NFE exome

AF:

0.00683

Gnomad4 OTH exome

AF:

0.00565

GnomAD4 genome

AF:

0.00411

AC:

626

AN:

152282

Hom.:

Cov.:

AF XY:

0.00420

AC XY:

313

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00385

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0119

Gnomad4 NFE

AF:

0.00565

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00464

Hom.:

Bravo

AF:

0.00374

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.000911

AC:

ESP6500EA

AF:

0.00582

AC:

ExAC

AF:

0.00341

AC:

413

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Dec 01, 2022

KCNK16: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.4

DANN

Benign

0.52

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0051

MetaSVM

Benign

-0.92

PROVEAN

Benign

-0.12

REVEL

Benign

0.010

Sift

Benign

0.34

Sift4G

Benign

0.41

Vest4

0.037

MVP

0.067

ClinPred

0.00083

GERP RS

-2.2

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