Genetic Variant KCNK10:p.Arg360Gln (chr14-88186088-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_138317.3(KCNK10):c.1079G>A(p.Arg360Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,458,976 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

KCNK10
NM_138317.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.88

Variant links:

Genes affected

KCNK10 (HGNC:6273): (potassium two pore domain channel subfamily K member 10) 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, and is stimulated strongly by arachidonic acid and to a lesser degree by membrane stretching, intracellular acidification, and general anaesthetics. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Sep 2008]

KCNK10 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
KCNK10	NM_138317.3 link	c.1079G>A	p.Arg360Gln	missense_variant	Exon 7 of 7	ENST00000319231.10	NP_612190.1	P57789-3
KCNK10	NM_138318.3 link	c.1079G>A	p.Arg360Gln	missense_variant	Exon 7 of 7		NP_612191.1	P57789-4
KCNK10	NM_021161.5 link	c.1064G>A	p.Arg355Gln	missense_variant	Exon 7 of 7		NP_066984.1	P57789-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNK10	ENST00000319231.10 link	c.1079G>A	p.Arg360Gln	missense_variant	Exon 7 of 7	1	NM_138317.3	ENSP00000312811.5	P57789-3
KCNK10	ENST00000312350.9 link	c.1079G>A	p.Arg360Gln	missense_variant	Exon 7 of 7	1		ENSP00000310568.5	P57789-4
KCNK10	ENST00000340700.9 link	c.1064G>A	p.Arg355Gln	missense_variant	Exon 7 of 7	1		ENSP00000343104.5	P57789-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000410

AC:

AN:

244198

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133040

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1458976

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725704

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1079G>A (p.R360Q) alteration is located in exon 7 (coding exon 7) of the KCNK10 gene. This alteration results from a G to A substitution at nucleotide position 1079, causing the arginine (R) at amino acid position 360 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

Pathogenic

0.65

BayesDel_addAF

Uncertain

0.097

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0098

T;.;.

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.057

MetaRNN

Uncertain

0.62

D;D;D

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.9

L;.;.

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.87

N;N;N

REVEL

Uncertain

0.32

Sift

Benign

0.050

D;D;D

Sift4G

Benign

0.10

T;T;T

Polyphen

1.0

D;.;.

Vest4

0.64

MutPred

0.46

Loss of sheet (P = 0.0037);.;.;

MVP

0.82

MPC

1.3

ClinPred

0.89

GERP RS

5.8

Varity_R

0.26

gMVP

0.92

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over