rs117478149

Variant summary

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

The NM_182982.3(GRK4):ā€‹c.517C>Gā€‹(p.Gln173Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,611,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

GRK4
NM_182982.3 missense

Scores

7
6
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.72
Variant links:
Genes affected
GRK4 (HGNC:4543): (G protein-coupled receptor kinase 4) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates the activated forms of G protein-coupled receptors thus initiating its deactivation. This gene has been linked to both genetic and acquired hypertension. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

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, 0.757

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GRK4NM_182982.3 linkc.517C>G p.Gln173Glu missense_variant Exon 6 of 16 ENST00000398052.9 NP_892027.2 P32298-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GRK4ENST00000398052.9 linkc.517C>G p.Gln173Glu missense_variant Exon 6 of 16 1 NM_182982.3 ENSP00000381129.4 P32298-1
GRK4ENST00000345167.10 linkc.421C>G p.Gln141Glu missense_variant Exon 5 of 15 1 ENSP00000264764.8 P32298-2
GRK4ENST00000504933.1 linkc.517C>G p.Gln173Glu missense_variant Exon 6 of 15 1 ENSP00000427445.1 P32298-4
GRK4ENST00000398051.8 linkc.421C>G p.Gln141Glu missense_variant Exon 5 of 14 1 ENSP00000381128.4 P32298-3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152138
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1458988
Hom.:
0
Cov.:
28
AF XY:
0.00000276
AC XY:
2
AN XY:
725894
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152138
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Uncertain
0.091
D
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.45
.;T;.;.
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D;D;D;D
M_CAP
Benign
0.010
T
MetaRNN
Pathogenic
0.76
D;D;D;D
MetaSVM
Benign
-1.2
T
MutationAssessor
Pathogenic
3.0
.;M;.;M
PrimateAI
Benign
0.47
T
PROVEAN
Uncertain
-2.7
D;D;D;D
REVEL
Uncertain
0.39
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Pathogenic
0.0010
D;D;D;D
Polyphen
1.0
D;D;D;D
Vest4
0.82
MutPred
0.47
.;Loss of MoRF binding (P = 0.0422);.;Loss of MoRF binding (P = 0.0422);
MVP
0.66
MPC
0.40
ClinPred
0.99
D
GERP RS
5.8
Varity_R
0.98
gMVP
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs117478149; hg19: chr4-3009536; API