Variant 6-39316274-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000437525.3(KCNK16):c.830C>A(p.Ala277Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 1,587,940 control chromosomes in the GnomAD database, including 210,679 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.59 ( 28607 hom., cov: 32)

Exomes 𝑓: 0.50 ( 182072 hom. )

Consequence

KCNK16
ENST00000437525.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.231

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2058849E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK16	NM_001135106.2 linkuse as main transcript	c.830C>A	p.Ala277Glu	missense_variant	5/5	ENST00000437525.3	NP_001128578.1
LOC105375047	XR_926774.3 linkuse as main transcript	n.269+2050G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK16	ENST00000437525.3 linkuse as main transcript	c.830C>A	p.Ala277Glu	missense_variant	5/5	1	NM_001135106.2	ENSP00000415375	P1	Q96T55-3

Frequencies

GnomAD3 genomes

AF:

0.593

AC:

90070

AN:

151914

Hom.:

28565

Cov.:

show subpopulations

Gnomad AFR

AF:

0.837

Gnomad AMI

AF:

0.555

Gnomad AMR

AF:

0.515

Gnomad ASJ

AF:

0.569

Gnomad EAS

AF:

0.462

Gnomad SAS

AF:

0.503

Gnomad FIN

AF:

0.502

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.493

Gnomad OTH

AF:

0.605

GnomAD3 exomes

AF:

0.505

AC:

102644

AN:

203114

Hom.:

26899

AF XY:

0.503

AC XY:

55212

AN XY:

109860

show subpopulations

Gnomad AFR exome

AF:

0.850

Gnomad AMR exome

AF:

0.433

Gnomad ASJ exome

AF:

0.552

Gnomad EAS exome

AF:

0.465

Gnomad SAS exome

AF:

0.497

Gnomad FIN exome

AF:

0.502

Gnomad NFE exome

AF:

0.488

Gnomad OTH exome

AF:

0.535

GnomAD4 exome

AF:

0.499

AC:

716971

AN:

1435908

Hom.:

182072

Cov.:

AF XY:

0.499

AC XY:

355070

AN XY:

711544

show subpopulations

Gnomad4 AFR exome

AF:

0.857

Gnomad4 AMR exome

AF:

0.446

Gnomad4 ASJ exome

AF:

0.554

Gnomad4 EAS exome

AF:

0.410

Gnomad4 SAS exome

AF:

0.497

Gnomad4 FIN exome

AF:

0.503

Gnomad4 NFE exome

AF:

0.490

Gnomad4 OTH exome

AF:

0.531

GnomAD4 genome

AF:

0.593

AC:

90155

AN:

152032

Hom.:

28607

Cov.:

AF XY:

0.592

AC XY:

43996

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.837

Gnomad4 AMR

AF:

0.515

Gnomad4 ASJ

AF:

0.569

Gnomad4 EAS

AF:

0.462

Gnomad4 SAS

AF:

0.502

Gnomad4 FIN

AF:

0.502

Gnomad4 NFE

AF:

0.493

Gnomad4 OTH

AF:

0.600

Alfa

AF:

0.537

Hom.:

8788

Bravo

AF:

0.607

TwinsUK

AF:

0.491

AC:

1820

ALSPAC

AF:

0.482

AC:

1858

ESP6500AA

AF:

0.833

AC:

3645

ESP6500EA

AF:

0.500

AC:

4293

ExAC

AF:

0.484

AC:

57757

Asia WGS

AF:

0.540

AC:

1874

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.39

DANN

Benign

0.60

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0000012

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

P;P;P;P;P

PROVEAN

Benign

0.0

REVEL

Benign

0.0080

Sift

Benign

0.11

Sift4G

Uncertain

0.051

Vest4

0.050

ClinPred

0.0029

GERP RS

1.9

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over