6-39317831-A-C

Position:

• chr6-39317831-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001135106.2(KCNK16):​c.450T>G​(p.His150Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.447

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18918297).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK16	NM_001135106.2	c.450T>G	p.His150Gln	missense_variant	3/5	ENST00000437525.3	NP_001128578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK16	ENST00000437525.3	c.450T>G	p.His150Gln	missense_variant	3/5	1	NM_001135106.2	ENSP00000415375.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Feb 07, 2023

The c.450T>G (p.H150Q) alteration is located in exon 3 (coding exon 3) of the KCNK16 gene. This alteration results from a T to G substitution at nucleotide position 450, causing the histidine (H) at amino acid position 150 to be replaced by a glutamine (Q). 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	0.16
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.0051	T;.;.;.;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.48	T;T;T;T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;.;L;L
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.4	N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.33	T;T;T;T;T
Sift4G	Benign	0.33	T;T;T;T;T
Polyphen		0.080	B;B;.;B;.
Vest4		0.27
MutPred		0.43		Gain of catalytic residue at H150 (P = 0.0155);Gain of catalytic residue at H150 (P = 0.0155);.;Gain of catalytic residue at H150 (P = 0.0155);Gain of catalytic residue at H150 (P = 0.0155);
MVP		0.24
MPC		0.23
ClinPred		0.23	T
GERP RS		1.4
Varity_R		0.079
gMVP		0.80

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: chr6-39285607;