1-160084095-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_004983.3(KCNJ9):ā€‹c.65A>Cā€‹(p.Gln22Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

KCNJ9
NM_004983.3 missense

Scores

5
9
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.90
Variant links:
Genes affected
KCNJ9 (HGNC:6270): (potassium inwardly rectifying channel subfamily J member 9) 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, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins. It associates with another G-protein-activated potassium channel to form a heteromultimeric pore-forming complex. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.758

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KCNJ9NM_004983.3 linkuse as main transcriptc.65A>C p.Gln22Pro missense_variant 2/3 ENST00000368088.4 NP_004974.2 Q92806

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KCNJ9ENST00000368088.4 linkuse as main transcriptc.65A>C p.Gln22Pro missense_variant 2/31 NM_004983.3 ENSP00000357067.3 Q92806

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1389512
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
685618
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 GeneticsDec 03, 2021The c.65A>C (p.Q22P) alteration is located in exon 2 (coding exon 1) of the KCNJ9 gene. This alteration results from a A to C substitution at nucleotide position 65, causing the glutamine (Q) at amino acid position 22 to be replaced by a proline (P). 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
0.19
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.010
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.57
D
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.81
T
M_CAP
Pathogenic
0.73
D
MetaRNN
Pathogenic
0.76
D
MetaSVM
Uncertain
0.34
D
MutationAssessor
Benign
1.6
L
PrimateAI
Pathogenic
0.92
D
PROVEAN
Uncertain
-4.3
D
REVEL
Pathogenic
0.76
Sift
Uncertain
0.021
D
Sift4G
Benign
0.10
T
Polyphen
0.99
D
Vest4
0.60
MutPred
0.30
Gain of glycosylation at Q22 (P = 0.0102);
MVP
0.67
ClinPred
1.0
D
GERP RS
4.3
Varity_R
0.85
gMVP
0.95

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-160053885; API