6-39319100-G-T

Position:

• chr6-39319100-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001135106.2(KCNK16):​c.247C>A​(p.Pro83Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNK16 NM_001135106.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.07

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK16	NM_001135106.2	c.247C>A	p.Pro83Thr	missense_variant	2/5	ENST00000437525.3	NP_001128578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK16	ENST00000437525.3	c.247C>A	p.Pro83Thr	missense_variant	2/5	1	NM_001135106.2	ENSP00000415375.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Aug 12, 2024

The c.247C>A (p.P83T) alteration is located in exon 2 (coding exon 2) of the KCNK16 gene. This alteration results from a C to A substitution at nucleotide position 247, causing the proline (P) at amino acid position 83 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	Uncertain	0.49
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T;.;.;.;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D;D;T;D;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.63	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;M;.;M;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.8	D;D;D;D;D
REVEL	Uncertain	0.34
Sift	Benign	0.10	T;T;D;D;T
Sift4G	Benign	0.20	T;T;T;T;T
Polyphen		0.47	P;P;.;B;.
Vest4		0.83
MutPred		0.35		Loss of ubiquitination at K79 (P = 0.0982);Loss of ubiquitination at K79 (P = 0.0982);.;Loss of ubiquitination at K79 (P = 0.0982);Loss of ubiquitination at K79 (P = 0.0982);
MVP		0.22
MPC		0.78
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.51
gMVP		0.84

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: chr6-39286876; COSMIC: COSV64677801; COSMIC: COSV64677801;