13-113667478-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002929.3(GRK1):​c.92G>T​(p.Arg31Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,656 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R31W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GRK1
NM_002929.3 missense

Scores

2
14
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.90

Publications

0 publications found
Variant links:
Genes affected
GRK1 (HGNC:10013): (G protein-coupled receptor kinase 1) 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 rhodopsin and initiates its deactivation. Defects in GRK1 are known to cause Oguchi disease 2 (also known as stationary night blindness Oguchi type-2). [provided by RefSeq, Jul 2008]
GRK1 Gene-Disease associations (from GenCC):
  • Oguchi disease
    Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
  • Oguchi disease-2
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GRK1NM_002929.3 linkc.92G>T p.Arg31Leu missense_variant Exon 1 of 7 ENST00000335678.7 NP_002920.1 Q15835
GRK1XM_047430493.1 linkc.-6-2209G>T intron_variant Intron 1 of 6 XP_047286449.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GRK1ENST00000335678.7 linkc.92G>T p.Arg31Leu missense_variant Exon 1 of 7 1 NM_002929.3 ENSP00000334876.5 Q15835

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458656
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
725322
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33424
American (AMR)
AF:
0.0000225
AC:
1
AN:
44390
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26056
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39576
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85860
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52640
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1110674
Other (OTH)
AF:
0.00
AC:
0
AN:
60268
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.66
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.030
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.58
D
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.73
T
M_CAP
Uncertain
0.26
D
MetaRNN
Uncertain
0.74
D
MetaSVM
Uncertain
-0.24
T
PhyloP100
4.9
PrimateAI
Uncertain
0.53
T
PROVEAN
Pathogenic
-5.1
D
REVEL
Uncertain
0.53
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0030
D
Polyphen
0.99
D
Vest4
0.53
MutPred
0.30
Gain of helix (P = 0.0199);
MVP
0.88
MPC
0.48
ClinPred
1.0
D
GERP RS
5.1
PromoterAI
0.0034
Neutral
Varity_R
0.69
gMVP
0.58
Mutation Taster
=28/72
disease causing

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

Other links and lift over

dbSNP: rs1243049516; hg19: chr13-114321793; API