1-160084074-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004983.3(KCNJ9):​c.44C>A​(p.Pro15Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

KCNJ9
NM_004983.3 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.781
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11581424).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KCNJ9NM_004983.3 linkc.44C>A p.Pro15Gln 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 linkc.44C>A p.Pro15Gln missense_variant 2/31 NM_004983.3 ENSP00000357067.3 Q92806

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
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 GeneticsJun 11, 2024The c.44C>A (p.P15Q) alteration is located in exon 2 (coding exon 1) of the KCNJ9 gene. This alteration results from a C to A substitution at nucleotide position 44, causing the proline (P) at amino acid position 15 to be replaced by a glutamine (Q). 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
0.069
BayesDel_addAF
Benign
-0.045
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.19
T
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.28
N
LIST_S2
Benign
0.17
T
M_CAP
Pathogenic
0.46
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
1.4
L
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-0.11
N
REVEL
Benign
0.11
Sift
Benign
0.29
T
Sift4G
Benign
0.30
T
Polyphen
0.0030
B
Vest4
0.18
MutPred
0.27
Loss of catalytic residue at P15 (P = 0.0051);
MVP
0.30
ClinPred
0.54
D
GERP RS
3.4
Varity_R
0.052
gMVP
0.80

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: chr1-160053864; API