6-39316287-C-T

Variant names:

• chr6-39316287-C-T
• rs185274513
• NM_001135106.2:c.817G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001135106.2(KCNK16):​c.817G>A​(p.Val273Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00574 in 1,597,838 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (5 hom., cov: 34)
  • Exomes 𝑓: 0.0059 (28 hom.)
• Consequence: KCNK16 NM_001135106.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.314
• Publications: 7 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 (MetaRNN=0.0051452518).
• BP6: Variant 6-39316287-C-T is Benign according to our data. Variant chr6-39316287-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2656535.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.817G>A	p.Val273Ile	missense	Exon 5 of 5	NP_001128578.1	Q96T55-3
	KCNK16	NM_001135105.2		c.661+495G>A		intron	N/A	NP_001128577.1	Q96T55-4
	KCNK16	NM_032115.4		c.802+15G>A		intron	N/A	NP_115491.1	Q96T55-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK16	ENST00000437525.3	TSL:1 MANE Select	c.817G>A	p.Val273Ile	missense	Exon 5 of 5	ENSP00000415375.2	Q96T55-3
	KCNK16	ENST00000425054.6	TSL:1	c.661+495G>A		intron	N/A	ENSP00000391498.2	Q96T55-4
	KCNK16	ENST00000373229.9	TSL:1	c.802+15G>A		intron	N/A	ENSP00000362326.5	Q96T55-1

Frequencies

GnomAD3 genomes AF: 0.00411 AC: 625 AN: 152164 Hom.: 5 Cov.: 34

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00379

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00565

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00357 AC: 776 AN: 217146 AF XY: 0.00359

Gnomad AFR exome AF: 0.000795

Gnomad AMR exome AF: 0.00244

Gnomad ASJ exome AF: 0.000108

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00825

Gnomad NFE exome AF: 0.00498

Gnomad OTH exome AF: 0.00409

GnomAD4 exome AF: 0.00591 AC: 8538 AN: 1445556 Hom.: 28 Cov.: 56 AF XY: 0.00573 AC XY: 4108 AN XY: 717342

African (AFR) AF: 0.000841 AC: 28 AN: 33312

American (AMR) AF: 0.00270 AC: 114 AN: 42240

Ashkenazi Jewish (ASJ) AF: 0.0000390 AC: 1 AN: 25672

East Asian (EAS) AF: 0.000128 AC: 5 AN: 39162

South Asian (SAS) AF: 0.00124 AC: 103 AN: 83120

European-Finnish (FIN) AF: 0.00769 AC: 397 AN: 51618

Middle Eastern (MID) AF: 0.00127 AC: 7 AN: 5518

European-Non Finnish (NFE) AF: 0.00683 AC: 7545 AN: 1105122

Other (OTH) AF: 0.00565 AC: 338 AN: 59792

GnomAD4 genome AF: 0.00411 AC: 626 AN: 152282 Hom.: 5 Cov.: 34 AF XY: 0.00420 AC XY: 313 AN XY: 74456

African (AFR) AF: 0.00101 AC: 42 AN: 41554

American (AMR) AF: 0.00385 AC: 59 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5176

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.0119 AC: 126 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00565 AC: 384 AN: 68014

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00445 Hom.: 3

Bravo AF: 0.00374

TwinsUK AF: 0.00593 AC: 22

ALSPAC AF: 0.00908 AC: 35

ESP6500AA AF: 0.000911 AC: 4

ESP6500EA AF: 0.00582 AC: 50

ExAC AF: 0.00341 AC: 413

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.4
DANN	Benign	0.52
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.0051	T
MetaSVM	Benign	-0.92	T
PhyloP100		0.31
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.010
Sift	Benign	0.34	T
Sift4G	Benign	0.41	T
Vest4		0.037
MVP		0.067
ClinPred		0.00083	T
GERP RS		-2.2
Mutation Taster		=100/0	polymorphism

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: rs185274513; hg19: chr6-39284063; COSMIC: COSV64679025; COSMIC: COSV64679025;