rs138573996

Variant names:

• chr6-39315040-G-A
• rs138573996
• ENST00000373229.9:c.892C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_032115.4(KCNK16):​c.892C>T​(p.Gln298*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0039 in 1,613,314 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0040 (26 hom.)
• Consequence: KCNK16 NM_032115.4 stop_gained
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.438
• Publications: 12 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 6-39315040-G-A is Benign according to our data. Variant chr6-39315040-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2656533.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032115.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK16	NM_032115.4		c.892C>T	p.Gln298*	stop_gained	Exon 6 of 6	NP_115491.1	Q96T55-1
	KCNK16	NM_001135107.2		c.751C>T	p.Gln251*	stop_gained	Exon 5 of 5	NP_001128579.1	Q96T55-5
	KCNK16	NM_001363784.1		c.556C>T	p.Gln186*	stop_gained	Exon 6 of 6	NP_001350713.1	D6RC57

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK16	ENST00000373229.9	TSL:1	c.892C>T	p.Gln298*	stop_gained	Exon 6 of 6	ENSP00000362326.5	Q96T55-1
	KCNK16	ENST00000373227.8	TSL:1	c.751C>T	p.Gln251*	stop_gained	Exon 5 of 5	ENSP00000362324.4	Q96T55-5
	KCNK16	ENST00000425054.6	TSL:1	c.*84C>T		3_prime_UTR	Exon 5 of 5	ENSP00000391498.2	Q96T55-4

Frequencies

GnomAD3 genomes AF: 0.00321 AC: 488 AN: 152214 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.00536

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00475

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.00385 AC: 965 AN: 250728 AF XY: 0.00402

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.00270

Gnomad ASJ exome AF: 0.000401

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00537

Gnomad NFE exome AF: 0.00453

Gnomad OTH exome AF: 0.00459

GnomAD4 exome AF: 0.00397 AC: 5798 AN: 1460982 Hom.: 26 Cov.: 65 AF XY: 0.00414 AC XY: 3007 AN XY: 726708

African (AFR) AF: 0.000598 AC: 20 AN: 33436

American (AMR) AF: 0.00289 AC: 129 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.000537 AC: 14 AN: 26054

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39680

South Asian (SAS) AF: 0.00652 AC: 562 AN: 86194

European-Finnish (FIN) AF: 0.00569 AC: 304 AN: 53410

Middle Eastern (MID) AF: 0.00382 AC: 22 AN: 5756

European-Non Finnish (NFE) AF: 0.00407 AC: 4529 AN: 1111474

Other (OTH) AF: 0.00358 AC: 216 AN: 60340

GnomAD4 genome AF: 0.00320 AC: 487 AN: 152332 Hom.: 2 Cov.: 33 AF XY: 0.00338 AC XY: 252 AN XY: 74484

African (AFR) AF: 0.000698 AC: 29 AN: 41570

American (AMR) AF: 0.00288 AC: 44 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00477 AC: 23 AN: 4824

European-Finnish (FIN) AF: 0.00536 AC: 57 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00475 AC: 323 AN: 68038

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00399 Hom.: 8

Bravo AF: 0.00271

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00441 AC: 17

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00244 AC: 21

ExAC AF: 0.00377 AC: 458

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00589

EpiControl AF: 0.00563

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.89
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.045	N
PhyloP100		0.44
Vest4		0.098
GERP RS		-0.34
Mutation Taster		=181/19	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs138573996; hg19: chr6-39282816;