Genetic Variant ENST00000373229.9:c.902C>A (chr6-39315030-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000373229.9(KCNK16):c.902C>A(p.Pro301His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 1,608,750 control chromosomes in the GnomAD database, including 213,657 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.59 ( 28434 hom., cov: 33)

Exomes 𝑓: 0.50 ( 185223 hom. )

Consequence

KCNK16
ENST00000373229.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.14

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.861604E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
KCNK16	NM_032115.4 link	c.902C>A	p.Pro301His	missense_variant	Exon 6 of 6	NP_115491.1	Q96T55-1
KCNK16	NM_001135107.2 link	c.761C>A	p.Pro254His	missense_variant	Exon 5 of 5	NP_001128579.1	Q96T55-5
KCNK16	NM_001363784.1 link	c.566C>A	p.Pro189His	missense_variant	Exon 6 of 6	NP_001350713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
KCNK16	ENST00000373229.9 link	c.902C>A	p.Pro301His	missense_variant	Exon 6 of 6	1	ENSP00000362326.5	Q96T55-1
KCNK16	ENST00000373227.8 link	c.761C>A	p.Pro254His	missense_variant	Exon 5 of 5	1	ENSP00000362324.4	Q96T55-5
KCNK16	ENST00000425054 link	c.*94C>A		3_prime_UTR_variant	Exon 5 of 5	1	ENSP00000391498.2	Q96T55-4
KCNK16	ENST00000507712.5 link	c.566C>A	p.Pro189His	missense_variant	Exon 6 of 6	3	ENSP00000423842.1	D6RC57

Frequencies

GnomAD3 genomes

AF:

0.592

AC:

89898

AN:

151964

Hom.:

28393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.831

Gnomad AMI

AF:

0.554

Gnomad AMR

AF:

0.514

Gnomad ASJ

AF:

0.569

Gnomad EAS

AF:

0.463

Gnomad SAS

AF:

0.503

Gnomad FIN

AF:

0.502

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.494

Gnomad OTH

AF:

0.604

GnomAD3 exomes

AF:

0.513

AC:

127782

AN:

248912

Hom.:

34198

AF XY:

0.509

AC XY:

68548

AN XY:

134560

show subpopulations

Gnomad AFR exome

AF:

0.843

Gnomad AMR exome

AF:

0.434

Gnomad ASJ exome

AF:

0.555

Gnomad EAS exome

AF:

0.473

Gnomad SAS exome

AF:

0.499

Gnomad FIN exome

AF:

0.507

Gnomad NFE exome

AF:

0.496

Gnomad OTH exome

AF:

0.538

GnomAD4 exome

AF:

0.500

AC:

728308

AN:

1456668

Hom.:

185223

Cov.:

AF XY:

0.500

AC XY:

361893

AN XY:

724062

show subpopulations

Gnomad4 AFR exome

AF:

0.851

Gnomad4 AMR exome

AF:

0.445

Gnomad4 ASJ exome

AF:

0.554

Gnomad4 EAS exome

AF:

0.412

Gnomad4 SAS exome

AF:

0.498

Gnomad4 FIN exome

AF:

0.504

Gnomad4 NFE exome

AF:

0.491

Gnomad4 OTH exome

AF:

0.531

GnomAD4 genome

AF:

0.592

AC:

89980

AN:

152082

Hom.:

28434

Cov.:

AF XY:

0.590

AC XY:

43876

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.831

Gnomad4 AMR

AF:

0.513

Gnomad4 ASJ

AF:

0.569

Gnomad4 EAS

AF:

0.463

Gnomad4 SAS

AF:

0.502

Gnomad4 FIN

AF:

0.502

Gnomad4 NFE

AF:

0.494

Gnomad4 OTH

AF:

0.598

Alfa

AF:

0.514

Hom.:

52571

Bravo

AF:

0.606

TwinsUK

AF:

0.491

AC:

1821

ALSPAC

AF:

0.484

AC:

1864

ESP6500AA

AF:

0.832

AC:

3665

ESP6500EA

AF:

0.501

AC:

4308

ExAC

AF:

0.523

AC:

63481

Asia WGS

AF:

0.538

AC:

1869

AN:

3476

EpiCase

AF:

0.515

EpiControl

AF:

0.508

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.49

DANN

Benign

0.87

DEOGEN2

Benign

0.0021

T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0085

LIST_S2

Benign

0.40

T;T;T

MetaRNN

Benign

9.9e-7

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.97

L;.;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.50

N;N;N

REVEL

Benign

0.036

Sift

Benign

0.25

T;T;D

Sift4G

Benign

0.10

T;D;D

Polyphen

0.0

B;.;B

Vest4

0.088

ClinPred

0.0053

GERP RS

0.093

Varity_R

0.11

Splicing

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