1-160042293-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_002241.5(KCNJ10):​c.240C>G​(p.Phe80Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,606 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F80V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

KCNJ10
NM_002241.5 missense

Scores

2
9
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.72
Variant links:
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 4 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, 7 uncertain in NM_002241.5
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCNJ10NM_002241.5 linkc.240C>G p.Phe80Leu missense_variant Exon 2 of 2 ENST00000644903.1 NP_002232.2 P78508

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KCNJ10ENST00000644903.1 linkc.240C>G p.Phe80Leu missense_variant Exon 2 of 2 NM_002241.5 ENSP00000495557.1 P78508

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250516
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135408
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:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461606
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727060
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:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.80
BayesDel_addAF
Uncertain
0.092
D
BayesDel_noAF
Uncertain
0.0
CADD
Uncertain
26
DANN
Uncertain
0.97
DEOGEN2
Uncertain
0.67
.;.;D;D;.;D;D
Eigen
Benign
0.015
Eigen_PC
Benign
0.042
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.82
T;T;.;.;D;.;D
M_CAP
Uncertain
0.087
D
MetaRNN
Uncertain
0.51
D;D;D;D;D;D;D
MetaSVM
Uncertain
-0.17
T
MutationAssessor
Benign
0.34
.;.;N;N;.;N;N
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-0.30
.;.;.;N;.;.;.
REVEL
Uncertain
0.54
Sift
Benign
0.94
.;.;.;T;.;.;.
Sift4G
Benign
0.80
.;.;.;T;.;.;.
Polyphen
0.99
.;.;D;D;.;D;D
Vest4
0.75
MutPred
0.63
Loss of MoRF binding (P = 0.3733);Loss of MoRF binding (P = 0.3733);Loss of MoRF binding (P = 0.3733);Loss of MoRF binding (P = 0.3733);.;Loss of MoRF binding (P = 0.3733);Loss of MoRF binding (P = 0.3733);
MVP
0.79
MPC
1.6
ClinPred
0.37
T
GERP RS
2.1
Varity_R
0.15
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: rs774758209; hg19: chr1-160012083; API