rs137853069
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP5
The NM_002241.5(KCNJ10):c.491C>T(p.Thr164Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
KCNJ10
NM_002241.5 missense
NM_002241.5 missense
Scores
3
8
3
Clinical Significance
Conservation
PhyloP100: 4.70
Genes affected
KCNJ10 (HGNC:6256): (potassium inwardly rectifying channel subfamily J member 10) This gene encodes a member of the inward rectifier-type potassium channel family, characterized by having a greater tendency to allow potassium to flow into, rather than out of, a cell. The encoded protein may form a heterodimer with another potassium channel protein and may be responsible for the potassium buffering action of glial cells in the brain. Mutations in this gene have been associated with seizure susceptibility of common idiopathic generalized epilepsy syndromes. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM1
?
In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 6 uncertain in NM_002241.5
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-160042042-G-A is Pathogenic according to our data. Variant chr1-160042042-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 7465.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-160042042-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNJ10 | NM_002241.5 | c.491C>T | p.Thr164Ile | missense_variant | 2/2 | ENST00000644903.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNJ10 | ENST00000644903.1 | c.491C>T | p.Thr164Ile | missense_variant | 2/2 | NM_002241.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Alfa
AF:
Hom.:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
EAST syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 12, 2010 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;D;.;D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
N;N;.;N;N
MutationTaster
Benign
A
PrimateAI
Uncertain
T
Polyphen
D;D;.;D;D
Vest4
0.19
MutPred
Loss of catalytic residue at T164 (P = 0.0926);Loss of catalytic residue at T164 (P = 0.0926);.;Loss of catalytic residue at T164 (P = 0.0926);Loss of catalytic residue at T164 (P = 0.0926);
MVP
0.89
MPC
1.5
ClinPred
D
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