6-39316877-A-G

Variant names:

• chr6-39316877-A-G
• NM_001135106.2:c.566T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001135106.2(KCNK16):​c.566T>C​(p.Met189Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KCNK16 NM_001135106.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.67
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2765246).

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.566T>C	p.Met189Thr	missense	Exon 4 of 5	NP_001128578.1	Q96T55-3
	KCNK16	NM_001135105.2		c.566T>C	p.Met189Thr	missense	Exon 4 of 5	NP_001128577.1	Q96T55-4
	KCNK16	NM_032115.4		c.566T>C	p.Met189Thr	missense	Exon 4 of 6	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.566T>C	p.Met189Thr	missense	Exon 4 of 5	ENSP00000415375.2	Q96T55-3
	KCNK16	ENST00000425054.6	TSL:1	c.566T>C	p.Met189Thr	missense	Exon 4 of 5	ENSP00000391498.2	Q96T55-4
	KCNK16	ENST00000373229.9	TSL:1	c.566T>C	p.Met189Thr	missense	Exon 4 of 6	ENSP00000362326.5	Q96T55-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Benign	0.90
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.92	L
PhyloP100		6.7
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.067	T
Polyphen		0.040	B
Vest4		0.58
MutPred		0.47		Gain of glycosylation at M189 (P = 0.0277)
MVP		0.27
MPC		0.45
ClinPred		0.85	D
GERP RS		4.3
Varity_R		0.41
gMVP		0.73
Mutation Taster		=58/42	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

hg19: chr6-39284653;