6-39316408-A-G

Variant names:

• chr6-39316408-A-G
• rs3734618
• NM_001135106.2:c.696T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.97
• Publications: 41 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 -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK16	NM_001135106.2	MANE Select	c.696T>C	p.Tyr232Tyr	synonymous	Exon 5 of 5	NP_001128578.1	Q96T55-3
	KCNK16	NM_032115.4		c.696T>C	p.Tyr232Tyr	synonymous	Exon 5 of 6	NP_115491.1	Q96T55-1
	KCNK16	NM_001135105.2		c.661+374T>C		intron	N/A	NP_001128577.1	Q96T55-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK16	ENST00000437525.3	TSL:1 MANE Select	c.696T>C	p.Tyr232Tyr	synonymous	Exon 5 of 5	ENSP00000415375.2	Q96T55-3
	KCNK16	ENST00000373229.9	TSL:1	c.696T>C	p.Tyr232Tyr	synonymous	Exon 5 of 6	ENSP00000362326.5	Q96T55-1
	KCNK16	ENST00000425054.6	TSL:1	c.661+374T>C		intron	N/A	ENSP00000391498.2	Q96T55-4

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92508 AN: 151928 Hom.: 30557 Cov.: 33

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

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.: 48 AF XY: 0.502 AC XY: 364373 AN XY: 725202

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

GnomAD4 genome AF: 0.609 AC: 92603 AN: 152046 Hom.: 30607 Cov.: 33 AF XY: 0.607 AC XY: 45138 AN XY: 74310

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	8.6
DANN	Benign	0.76
PhyloP100		3.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3734618; hg19: chr6-39284184; COSMIC: COSV64678340; COSMIC: COSV64678340;