chr21-38299383-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_170736.3(KCNJ15):ā€‹c.122A>Gā€‹(p.Asp41Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000929 in 1,614,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000075 ( 0 hom. )

Consequence

KCNJ15
NM_170736.3 missense

Scores

3
9
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.23
Variant links:
Genes affected
KCNJ15 (HGNC:6261): (potassium inwardly rectifying channel subfamily J member 15) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Eight transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Feb 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33839512).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KCNJ15NM_170736.3 linkuse as main transcriptc.122A>G p.Asp41Gly missense_variant 3/3 ENST00000398938.7 NP_733932.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KCNJ15ENST00000398938.7 linkuse as main transcriptc.122A>G p.Asp41Gly missense_variant 3/31 NM_170736.3 ENSP00000381911 P1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152218
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000752
AC:
11
AN:
1461890
Hom.:
0
Cov.:
32
AF XY:
0.00000550
AC XY:
4
AN XY:
727246
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:
0.00000899
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152218
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 04, 2023The c.122A>G (p.D41G) alteration is located in exon 3 (coding exon 1) of the KCNJ15 gene. This alteration results from a A to G substitution at nucleotide position 122, causing the aspartic acid (D) at amino acid position 41 to be replaced by a glycine (G). 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
Benign
0.22
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.18
.;.;.;.;.;.;T;T;.;T;T;T;T;.;T;T;T;T
Eigen
Benign
0.18
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.90
.;.;.;.;.;D;.;D;D;.;.;.;.;D;.;.;D;D
M_CAP
Benign
0.045
D
MetaRNN
Benign
0.34
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
0.23
D
MutationAssessor
Benign
0.65
.;.;.;.;.;.;N;N;.;.;N;N;N;.;N;N;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.66
T
PROVEAN
Pathogenic
-7.0
D;D;D;D;D;D;.;.;D;N;N;N;N;N;N;N;N;N
REVEL
Uncertain
0.45
Sift
Pathogenic
0.0
D;D;D;D;D;D;.;.;D;T;T;T;T;T;T;T;T;T
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;T;T;D;T;T;T;T;T;T;T;T;T
Polyphen
0.99
.;.;.;.;.;.;D;D;.;.;D;D;D;.;D;D;.;.
Vest4
0.21, 0.18, 0.20, 0.20, 0.18
MutPred
0.47
Loss of stability (P = 0.0068);Loss of stability (P = 0.0068);Loss of stability (P = 0.0068);Loss of stability (P = 0.0068);Loss of stability (P = 0.0068);Loss of stability (P = 0.0068);Loss of stability (P = 0.0068);Loss of stability (P = 0.0068);Loss of stability (P = 0.0068);Loss of stability (P = 0.0068);Loss of stability (P = 0.0068);Loss of stability (P = 0.0068);Loss of stability (P = 0.0068);Loss of stability (P = 0.0068);Loss of stability (P = 0.0068);Loss of stability (P = 0.0068);Loss of stability (P = 0.0068);Loss of stability (P = 0.0068);
MVP
0.86
MPC
1.5
ClinPred
0.92
D
GERP RS
5.1
Varity_R
0.52
gMVP
0.88

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: rs199852196; hg19: chr21-39671305; API