14-88186088-C-T

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

6
4
9

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]

Genome browser will be placed here

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
KCNK10NM_138317.3 linkc.1079G>A p.Arg360Gln missense_variant Exon 7 of 7 ENST00000319231.10 NP_612190.1 P57789-3
KCNK10NM_138318.3 linkc.1079G>A p.Arg360Gln missense_variant Exon 7 of 7 NP_612191.1 P57789-4
KCNK10NM_021161.5 linkc.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 Appris UniProt
KCNK10ENST00000319231.10 linkc.1079G>A p.Arg360Gln missense_variant Exon 7 of 7 1 NM_138317.3 ENSP00000312811.5 P57789-3
KCNK10ENST00000312350.9 linkc.1079G>A p.Arg360Gln missense_variant Exon 7 of 7 1 ENSP00000310568.5 P57789-4
KCNK10ENST00000340700.9 linkc.1064G>A p.Arg355Gln missense_variant Exon 7 of 7 1 ENSP00000343104.5 P57789-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000410
AC:
1
AN:
244198
Hom.:
0
AF XY:
0.00
AC XY:
0
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:
7
AN:
1458976
Hom.:
0
Cov.:
35
AF XY:
0.00000138
AC XY:
1
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.:
32
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
D
BayesDel_noAF
Benign
-0.10
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.0098
T;.;.
Eigen
Pathogenic
0.82
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.91
D;D;D
M_CAP
Benign
0.057
D
MetaRNN
Uncertain
0.62
D;D;D
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.9
L;.;.
PrimateAI
Pathogenic
0.86
D
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
D
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.

Other links and lift over

dbSNP: rs1348379470; hg19: chr14-88652432; COSMIC: COSV100067324; API