chr2-26692892-T-C
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_002246.3(KCNK3):c.17T>C(p.Val6Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,417,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000016 ( 0 hom. )
Consequence
KCNK3
NM_002246.3 missense
NM_002246.3 missense
Scores
2
3
13
Clinical Significance
Conservation
PhyloP100: 3.30
Publications
0 publications found
Genes affected
KCNK3 (HGNC:6278): (potassium two pore domain channel subfamily K member 3) This gene encodes a member of the superfamily of potassium channel proteins that contain two pore-forming P domains. The encoded protein is an outwardly rectifying channel that is sensitive to changes in extracellular pH and is inhibited by extracellular acidification. Also referred to as an acid-sensitive potassium channel, it is activated by the anesthetics halothane and isoflurane. Although three transcripts are detected in northern blots, there is currently no sequence available to confirm transcript variants for this gene. [provided by RefSeq, Aug 2008]
KCNK3 Gene-Disease associations (from GenCC):
- pulmonary arterial hypertensionInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- pulmonary hypertension, primary, 4Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- heritable pulmonary arterial hypertensionInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM1
In a mutagenesis_site No effect on channel basal activity. (size 0) in uniprot entity KCNK3_HUMAN
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21881151).
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_002246.3. You can select a different transcript below to see updated ACMG assignments.
Frequencies
GnomAD3 genomes 0.00000664 AC: 1AN: 150500Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
150500
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000247 AC: 2AN: 80868 AF XY: 0.0000434 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
80868
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000158 AC: 2AN: 1267074Hom.: 0 Cov.: 31 AF XY: 0.00000162 AC XY: 1AN XY: 618326 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1267074
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
618326
show subpopulations
African (AFR)
AF:
AC:
0
AN:
26236
American (AMR)
AF:
AC:
0
AN:
25834
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
22074
East Asian (EAS)
AF:
AC:
0
AN:
27668
South Asian (SAS)
AF:
AC:
0
AN:
65012
European-Finnish (FIN)
AF:
AC:
0
AN:
35638
Middle Eastern (MID)
AF:
AC:
0
AN:
3672
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1009310
Other (OTH)
AF:
AC:
0
AN:
51630
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.650
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000664 AC: 1AN: 150500Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1AN XY: 73486 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
150500
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
73486
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41082
American (AMR)
AF:
AC:
0
AN:
15152
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3462
East Asian (EAS)
AF:
AC:
0
AN:
5068
South Asian (SAS)
AF:
AC:
0
AN:
4806
European-Finnish (FIN)
AF:
AC:
0
AN:
10060
Middle Eastern (MID)
AF:
AC:
0
AN:
308
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67584
Other (OTH)
AF:
AC:
0
AN:
2066
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Pulmonary hypertension, primary, 4 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
PhyloP100
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of stability (P = 0.0232)
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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