Genetic Variant KCNK16:p.Arg160His (chr6-39317802-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001135106.2(KCNK16):c.479G>A(p.Arg160His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,603,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R160C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

KCNK16
NM_001135106.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0420

Publications

2 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.048633516).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135106.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCNK16	NM_001135106.2	MANE Select	c.479G>A	p.Arg160His	missense	Exon 3 of 5	NP_001128578.1	Q96T55-3
KCNK16	NM_001135105.2		c.479G>A	p.Arg160His	missense	Exon 3 of 5	NP_001128577.1	Q96T55-4
KCNK16	NM_032115.4		c.479G>A	p.Arg160His	missense	Exon 3 of 6	NP_115491.1	Q96T55-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCNK16	ENST00000437525.3	TSL:1 MANE Select	c.479G>A	p.Arg160His	missense	Exon 3 of 5	ENSP00000415375.2	Q96T55-3
KCNK16	ENST00000425054.6	TSL:1	c.479G>A	p.Arg160His	missense	Exon 3 of 5	ENSP00000391498.2	Q96T55-4
KCNK16	ENST00000373229.9	TSL:1	c.479G>A	p.Arg160His	missense	Exon 3 of 6	ENSP00000362326.5	Q96T55-1

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000772

AC:

AN:

233040

AF XY:

0.0000715

show subpopulations

Gnomad AFR exome

AF:

0.0000675

Gnomad AMR exome

AF:

0.0000311

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000134

Gnomad OTH exome

AF:

0.000175

GnomAD4 exome

AF:

0.000111

AC:

161

AN:

1451352

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

721058

show subpopulations

African (AFR)

AF:

0.000150

AC:

AN:

33342

American (AMR)

AF:

0.00

AC:

AN:

42796

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25746

East Asian (EAS)

AF:

0.0000508

AC:

AN:

39378

South Asian (SAS)

AF:

0.0000237

AC:

AN:

84266

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52902

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5710

European-Non Finnish (NFE)

AF:

0.000128

AC:

142

AN:

1107204

Other (OTH)

AF:

0.000167

AC:

AN:

60008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000118

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41584

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68040

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000114

Hom.:

Bravo

AF:

0.0000907

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0045

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.31

M_CAP

Benign

0.010

MetaRNN

Benign

0.049

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.45

PhyloP100

0.042

PrimateAI

Benign

0.19

PROVEAN

Benign

-1.3

REVEL

Benign

0.026

Sift

Benign

0.12

Sift4G

Benign

0.066

Polyphen

0.0

Vest4

0.25

MVP

0.29

MPC

0.24

ClinPred

0.069

GERP RS

1.3

Varity_R

0.037

gMVP

0.56

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over