NM_002929.3:c.178A>C

Variant summary

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

The NM_002929.3(GRK1):​c.178A>C​(p.Ser60Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GRK1
NM_002929.3 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.60
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]

Genome browser will be placed here

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=0.13482943).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GRK1NM_002929.3 linkc.178A>C p.Ser60Arg missense_variant Exon 1 of 7 ENST00000335678.7 NP_002920.1 Q15835
GRK1XM_047430493.1 linkc.-6-2123A>C 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.178A>C p.Ser60Arg missense_variant Exon 1 of 7 1 NM_002929.3 ENSP00000334876.5 Q15835

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000803
AC:
2
AN:
249006
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135206
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461288
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
726924
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000468
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Feb 26, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.178A>C (p.S60R) alteration is located in exon 1 (coding exon 1) of the GRK1 gene. This alteration results from a A to C substitution at nucleotide position 178, causing the serine (S) at amino acid position 60 to be replaced by an arginine (R). 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
0.25
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
15
DANN
Benign
0.95
DEOGEN2
Benign
0.21
T
Eigen
Benign
-0.75
Eigen_PC
Benign
-0.78
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.67
T
M_CAP
Benign
0.0038
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-0.94
T
PrimateAI
Benign
0.40
T
PROVEAN
Uncertain
-2.8
D
REVEL
Benign
0.037
Sift
Benign
0.043
D
Sift4G
Benign
0.11
T
Polyphen
0.0020
B
Vest4
0.22
MutPred
0.51
Gain of catalytic residue at L63 (P = 0);
MVP
0.43
MPC
0.10
ClinPred
0.62
D
GERP RS
2.7
Varity_R
0.31
gMVP
0.53

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.

Other links and lift over

dbSNP: rs1235802388; hg19: chr13-114321879; API