6-39316877-A-G

Position:

• chr6-39316877-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 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

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 Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK16	NM_001135106.2	c.566T>C	p.Met189Thr	missense_variant	4/5	ENST00000437525.3	NP_001128578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK16	ENST00000437525.3	c.566T>C	p.Met189Thr	missense_variant	4/5	1	NM_001135106.2	ENSP00000415375.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 19, 2023

The c.566T>C (p.M189T) alteration is located in exon 4 (coding exon 4) of the KCNK16 gene. This alteration results from a T to C substitution at nucleotide position 566, causing the methionine (M) at amino acid position 189 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.28	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.92	L;L;.;L;L
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.8	D;D;D;D;D
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D;T;D;D;D
Sift4G	Benign	0.067	T;T;T;T;D
Polyphen		0.040	B;P;.;B;.
Vest4		0.58
MutPred		0.47		Gain of glycosylation at M189 (P = 0.0277);Gain of glycosylation at M189 (P = 0.0277);.;Gain of glycosylation at M189 (P = 0.0277);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-39284653;