Genetic Variant KCNK16:p.Tyr232Tyr (chr6-39316408-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001135106.2(KCNK16):c.696T>C(p.Tyr232Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 1,610,556 control chromosomes in the GnomAD database, including 218,899 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.61 ( 30607 hom., cov: 33)

Exomes 𝑓: 0.50 ( 188292 hom. )

Consequence

KCNK16
NM_001135106.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.97

Publications

41 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.22).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK16	NM_001135106.2 link	c.696T>C	p.Tyr232Tyr	synonymous_variant	Exon 5 of 5	ENST00000437525.3	NP_001128578.1	Q96T55-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK16	ENST00000437525.3 link	c.696T>C	p.Tyr232Tyr	synonymous_variant	Exon 5 of 5	1	NM_001135106.2	ENSP00000415375.2		Q96T55-3

Frequencies

GnomAD3 genomes

AF:

0.609

AC:

92508

AN:

151928

Hom.:

30557

Cov.:

show subpopulations

Gnomad AFR

AF:

0.887

Gnomad AMI

AF:

0.555

Gnomad AMR

AF:

0.522

Gnomad ASJ

AF:

0.601

Gnomad EAS

AF:

0.463

Gnomad SAS

AF:

0.502

Gnomad FIN

AF:

0.503

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.495

Gnomad OTH

AF:

0.619

GnomAD2 exomes

AF:

0.519

AC:

126896

AN:

244382

AF XY:

0.514

show subpopulations

Gnomad AFR exome

AF:

0.898

Gnomad AMR exome

AF:

0.439

Gnomad ASJ exome

AF:

0.593

Gnomad EAS exome

AF:

0.471

Gnomad FIN exome

AF:

0.505

Gnomad NFE exome

AF:

0.497

Gnomad OTH exome

AF:

0.544

GnomAD4 exome

AF:

0.503

AC:

733437

AN:

1458510

Hom.:

188292

Cov.:

AF XY:

0.502

AC XY:

364373

AN XY:

725202

show subpopulations

African (AFR)

AF:

0.907

AC:

30338

AN:

33448

American (AMR)

AF:

0.450

AC:

19945

AN:

44288

Ashkenazi Jewish (ASJ)

AF:

0.590

AC:

15356

AN:

26044

East Asian (EAS)

AF:

0.412

AC:

16327

AN:

39590

South Asian (SAS)

AF:

0.497

AC:

42573

AN:

85736

European-Finnish (FIN)

AF:

0.504

AC:

26834

AN:

53234

Middle Eastern (MID)

AF:

0.626

AC:

3578

AN:

5720

European-Non Finnish (NFE)

AF:

0.492

AC:

546094

AN:

1110208

Other (OTH)

AF:

0.538

AC:

32392

AN:

60242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

18966

37932

56898

75864

94830

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16070

32140

48210

64280

80350

<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:

0.609

AC:

92603

AN:

152046

Hom.:

30607

Cov.:

AF XY:

0.607

AC XY:

45138

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.887

AC:

36804

AN:

41510

American (AMR)

AF:

0.522

AC:

7978

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.601

AC:

2086

AN:

3468

East Asian (EAS)

AF:

0.464

AC:

2380

AN:

5134

South Asian (SAS)

AF:

0.501

AC:

2413

AN:

4814

European-Finnish (FIN)

AF:

0.503

AC:

5317

AN:

10580

Middle Eastern (MID)

AF:

0.653

AC:

192

AN:

294

European-Non Finnish (NFE)

AF:

0.495

AC:

33637

AN:

67944

Other (OTH)

AF:

0.613

AC:

1294

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1656

3312

4967

6623

8279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

732

1464

2196

2928

3660

<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:

0.533

Hom.:

44533

Bravo

AF:

0.625

Asia WGS

AF:

0.541

AC:

1878

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.22

CADD

Benign

8.6

(source)

DANN

Benign

0.76

PhyloP100

3.0

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over