Genetic Variant NM_001135106.2:c.830C>A (chr6-39316274-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001135106.2(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. 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.

Frequency

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

Exomes 𝑓: 0.50 ( 182072 hom. )

Consequence

KCNK16
NM_001135106.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.231

Publications

107 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 -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.

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.830C>A	p.Ala277Glu	missense	Exon 5 of 5	NP_001128578.1	Q96T55-3
KCNK16	NM_001135105.2		c.661+508C>A		intron	N/A	NP_001128577.1	Q96T55-4
KCNK16	NM_032115.4		c.802+28C>A		intron	N/A	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.830C>A	p.Ala277Glu	missense	Exon 5 of 5	ENSP00000415375.2	Q96T55-3
KCNK16	ENST00000425054.6	TSL:1	c.661+508C>A		intron	N/A	ENSP00000391498.2	Q96T55-4
KCNK16	ENST00000373229.9	TSL:1	c.802+28C>A		intron	N/A	ENSP00000362326.5	Q96T55-1

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

GnomAD2 exomes

AF:

0.505

AC:

102644

AN:

203114

AF XY:

0.503

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 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

African (AFR)

AF:

0.857

AC:

28402

AN:

33140

American (AMR)

AF:

0.446

AC:

18085

AN:

40570

Ashkenazi Jewish (ASJ)

AF:

0.554

AC:

14143

AN:

25536

East Asian (EAS)

AF:

0.410

AC:

15894

AN:

38754

South Asian (SAS)

AF:

0.497

AC:

40847

AN:

82216

European-Finnish (FIN)

AF:

0.503

AC:

25642

AN:

50958

Middle Eastern (MID)

AF:

0.617

AC:

3293

AN:

5338

European-Non Finnish (NFE)

AF:

0.490

AC:

539099

AN:

1099966

Other (OTH)

AF:

0.531

AC:

31566

AN:

59430

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

19359

38718

58078

77437

96796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15932

31864

47796

63728

79660

<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:

0.593

AC:

90155

AN:

152032

Hom.:

28607

Cov.:

AF XY:

0.592

AC XY:

43996

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.837

AC:

34717

AN:

41486

American (AMR)

AF:

0.515

AC:

7874

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.569

AC:

1975

AN:

3472

East Asian (EAS)

AF:

0.462

AC:

2371

AN:

5134

South Asian (SAS)

AF:

0.502

AC:

2409

AN:

4800

European-Finnish (FIN)

AF:

0.502

AC:

5324

AN:

10596

Middle Eastern (MID)

AF:

0.653

AC:

192

AN:

294

European-Non Finnish (NFE)

AF:

0.493

AC:

33529

AN:

67942

Other (OTH)

AF:

0.600

AC:

1259

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1723

3446

5169

6892

8615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

726

1452

2178

2904

3630

<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:

0.542

Hom.:

12918

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.39

(source)

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

PhyloP100

-0.23

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

Mutation Taster

=93/7

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over