ENST00000373229.9:c.902C>A

Variant names:

• chr6-39315030-G-T
• rs11756091
• ENST00000373229.9:c.902C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 14/19 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 (28434 hom., cov: 33)
  • Exomes 𝑓: 0.50 (185223 hom.)
• Consequence: KCNK16 ENST00000373229.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 50 publications found

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]

LOC105375047 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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	MANE	Protein	UniProt
KCNK16	NM_032115.4	c.902C>A	p.Pro301His	missense_variant	Exon 6 of 6		NP_115491.1
KCNK16	NM_001135107.2	c.761C>A	p.Pro254His	missense_variant	Exon 5 of 5		NP_001128579.1
KCNK16	NM_001363784.1	c.566C>A	p.Pro189His	missense_variant	Exon 6 of 6		NP_001350713.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89898 AN: 151964 Hom.: 28393 Cov.: 33

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

GnomAD2 exomes AF: 0.513 AC: 127782 AN: 248912 AF XY: 0.509

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 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.: 55 AF XY: 0.500 AC XY: 361893 AN XY: 724062

African (AFR) AF: 0.851 AC: 28272 AN: 33228

American (AMR) AF: 0.445 AC: 19631 AN: 44140

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 14350 AN: 25884

East Asian (EAS) AF: 0.412 AC: 16320 AN: 39566

South Asian (SAS) AF: 0.498 AC: 42741 AN: 85894

European-Finnish (FIN) AF: 0.504 AC: 26904 AN: 53338

Middle Eastern (MID) AF: 0.623 AC: 3568 AN: 5730

European-Non Finnish (NFE) AF: 0.491 AC: 544633 AN: 1108816

Other (OTH) AF: 0.531 AC: 31889 AN: 60072

GnomAD4 genome AF: 0.592 AC: 89980 AN: 152082 Hom.: 28434 Cov.: 33 AF XY: 0.590 AC XY: 43876 AN XY: 74322

African (AFR) AF: 0.831 AC: 34493 AN: 41528

American (AMR) AF: 0.513 AC: 7841 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1973 AN: 3466

East Asian (EAS) AF: 0.463 AC: 2385 AN: 5152

South Asian (SAS) AF: 0.502 AC: 2418 AN: 4820

European-Finnish (FIN) AF: 0.502 AC: 5308 AN: 10570

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33601 AN: 67952

Other (OTH) AF: 0.598 AC: 1264 AN: 2112

Alfa AF: 0.523 Hom.: 105390

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	T
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	N
LIST_S2	Benign	0.40	T;T;T
MetaRNN	Benign	9.9e-7	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.97	L;.;.
PhyloP100		-1.1
PrimateAI	Benign	0.24	T
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	T
GERP RS		0.093
Varity_R		0.11
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11756091; hg19: chr6-39282806; COSMIC: COSV64677699; COSMIC: COSV64677699;