6-39316408-A-G

Position:

• chr6-39316408-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
KCNK16	NM_001135106.2	c.696T>C	p.Tyr232Tyr	synonymous_variant	5/5	ENST00000437525.3	NP_001128578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK16	ENST00000437525.3	c.696T>C	p.Tyr232Tyr	synonymous_variant	5/5	1	NM_001135106.2	ENSP00000415375.2

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

GnomAD3 exomes AF: 0.519 AC: 126896 AN: 244382 Hom.: 34479 AF XY: 0.514 AC XY: 67987 AN XY: 132286

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 SAS exome AF: 0.500

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

Gnomad4 AFR exome AF: 0.907

Gnomad4 AMR exome AF: 0.450

Gnomad4 ASJ exome AF: 0.590

Gnomad4 EAS exome AF: 0.412

Gnomad4 SAS exome AF: 0.497

Gnomad4 FIN exome AF: 0.504

Gnomad4 NFE exome AF: 0.492

Gnomad4 OTH exome AF: 0.538

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

Gnomad4 AFR AF: 0.887

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.613

Alfa AF: 0.524 Hom.: 34941

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
DANN	Benign	0.76

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

LitVar

Other links and lift over

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