Variant 3-141780636-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_139209.3(GRK7):c.875G>A(p.Arg292Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000619 in 1,614,216 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 1 hom. )

Consequence

GRK7
NM_139209.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.76

Variant links:

Genes affected

GRK7 (HGNC:17031): (G protein-coupled receptor kinase 7) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. It is specifically expressed in the retina and the encoded protein has been shown to phosphorylate cone opsins and initiate their deactivation. [provided by RefSeq, Jul 2008]

GRK7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRK7	NM_139209.3 linkuse as main transcript	c.875G>A	p.Arg292Gln	missense_variant	4/6	ENST00000682958.1
GRK7	XM_047447449.1 linkuse as main transcript	c.875G>A	p.Arg292Gln	missense_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRK7	ENST00000682958.1 linkuse as main transcript	c.875G>A	p.Arg292Gln	missense_variant	4/6		NM_139209.3	P1
GRK7	ENST00000264952.2 linkuse as main transcript	c.875G>A	p.Arg292Gln	missense_variant	2/4	1		P1

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

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:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000796

AC:

AN:

251410

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.0000867

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000376

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000956

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000629

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.000295

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000582

Hom.:

Bravo

AF:

0.000378

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

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 submitter

clinical testing

Ambry Genetics

Aug 17, 2021

The c.875G>A (p.R292Q) alteration is located in exon 2 (coding exon 2) of the GRK7 gene. This alteration results from a G to A substitution at nucleotide position 875, causing the arginine (R) at amino acid position 292 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Uncertain

0.12

Cadd

Uncertain

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.052

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-0.36

MutationAssessor

Benign

0.91

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.57

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.022

Polyphen

1.0

Vest4

0.69

MVP

0.93

MPC

0.75

ClinPred

0.40

GERP RS

5.1

Varity_R

0.89

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over