Variant 3-141778685-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_139209.3(GRK7):c.401G>A(p.Cys134Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000483 in 1,613,658 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 (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

GRK7
NM_139209.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.11

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:

ENSG00000285558 (HGNC:):

ENSG00000285558 links:

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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=0.07317361).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRK7	NM_139209.3 linkuse as main transcript	c.401G>A	p.Cys134Tyr	missense_variant	3/6	ENST00000682958.1	NP_631948.1	Q8WTQ7
GRK7	XM_047447449.1 linkuse as main transcript	c.401G>A	p.Cys134Tyr	missense_variant	4/7		XP_047303405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GRK7	ENST00000682958.1 linkuse as main transcript	c.401G>A	p.Cys134Tyr	missense_variant	3/6		NM_139209.3	ENSP00000508022.1	Q8WTQ7
GRK7	ENST00000264952.2 linkuse as main transcript	c.401G>A	p.Cys134Tyr	missense_variant	1/4	1		ENSP00000264952.2	Q8WTQ7
ENSG00000285558	ENST00000648835.1 linkuse as main transcript	n.44-1689G>A		intron_variant				ENSP00000498049.1	A0A3B3IU32

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000439

AC:

AN:

250364

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135426

show subpopulations

Gnomad AFR exome

AF:

0.000618

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1461290

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726852

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000276

AC:

AN:

152368

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.00101

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000727

Hom.:

Bravo

AF:

0.000348

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000576

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jun 02, 2023

The c.401G>A (p.C134Y) alteration is located in exon 1 (coding exon 1) of the GRK7 gene. This alteration results from a G to A substitution at nucleotide position 401, causing the cysteine (C) at amino acid position 134 to be replaced by a tyrosine (Y). 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

0.29

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.20

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.20

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.71

M_CAP

Benign

0.0059

MetaRNN

Benign

0.073

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.15

Sift

Uncertain

0.027

Sift4G

Benign

0.18

Polyphen

0.036

Vest4

0.29

MVP

0.47

MPC

0.48

ClinPred

0.14

GERP RS

4.7

Varity_R

0.50

gMVP

0.86

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.

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