13-113667849-G-T

Variant summary

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

The NM_002929.3(GRK1):​c.463G>T​(p.Ala155Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A155V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

GRK1
NM_002929.3 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.467
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]

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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=0.07667625).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GRK1NM_002929.3 linkuse as main transcriptc.463G>T p.Ala155Ser missense_variant 1/7 ENST00000335678.7
GRK1XM_047430493.1 linkuse as main transcriptc.-6-1838G>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GRK1ENST00000335678.7 linkuse as main transcriptc.463G>T p.Ala155Ser missense_variant 1/71 NM_002929.3 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 24, 2022The c.463G>T (p.A155S) alteration is located in exon 1 (coding exon 1) of the GRK1 gene. This alteration results from a G to T substitution at nucleotide position 463, causing the alanine (A) at amino acid position 155 to be replaced by a serine (S). 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
0.076
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
16
DANN
Benign
0.97
DEOGEN2
Benign
0.038
T
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.075
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.61
T
M_CAP
Benign
0.0052
T
MetaRNN
Benign
0.077
T
MetaSVM
Benign
-0.90
T
MutationTaster
Benign
0.97
N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
0.80
N
REVEL
Benign
0.026
Sift
Benign
0.31
T
Sift4G
Benign
0.72
T
Polyphen
0.0050
B
Vest4
0.13
MutPred
0.32
Gain of catalytic residue at A160 (P = 0.0245);
MVP
0.54
MPC
0.086
ClinPred
0.42
T
GERP RS
3.3
Varity_R
0.080
gMVP
0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-114322164; API