10-86658579-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_033282.4(OPN4):​c.520C>G​(p.Arg174Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. R174C) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)

Consequence

OPN4
NM_033282.4 missense

Scores

4
11
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.18
Variant links:
Genes affected
OPN4 (HGNC:14449): (opsin 4) Opsins are members of the guanine nucleotide-binding protein (G protein)-coupled receptor superfamily. This gene encodes a photoreceptive opsin protein that is expressed within the ganglion and amacrine cell layers of the retina. In mouse, retinal ganglion cell axons expressing this gene projected to the suprachiasmatic nucleus and other brain nuclei involved in circadian photoentrainment. In mouse, this protein is coupled to a transient receptor potential (TRP) ion channel through a G protein signaling pathway and produces a physiologic light response via membrane depolarization and increased intracellular calcium. The protein functions as a sensory photopigment and may also have photoisomerase activity. Experiments with knockout mice indicate that this gene attenuates, but does not abolish, photoentrainment. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OPN4NM_033282.4 linkc.520C>G p.Arg174Gly missense_variant Exon 4 of 10 ENST00000241891.10 NP_150598.1 Q9UHM6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OPN4ENST00000241891.10 linkc.520C>G p.Arg174Gly missense_variant Exon 4 of 10 1 NM_033282.4 ENSP00000241891.5 Q9UHM6-1
ENSG00000289258ENST00000443292.2 linkc.553C>G p.Arg185Gly missense_variant Exon 5 of 18 1 ENSP00000393132.2 C9JWU6

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152260
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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
GnomAD4 exome
Cov.:
32
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152260
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.47
.;T;.
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.97
D;D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.80
D;D;D
MetaSVM
Benign
-0.39
T
MutationAssessor
Pathogenic
3.1
.;M;.
PrimateAI
Benign
0.27
T
PROVEAN
Pathogenic
-5.4
D;D;D
REVEL
Uncertain
0.38
Sift
Uncertain
0.0030
D;D;D
Sift4G
Uncertain
0.0050
D;D;D
Polyphen
0.93
P;P;P
Vest4
0.76
MutPred
0.72
Gain of catalytic residue at T184 (P = 0.1139);.;Gain of catalytic residue at T184 (P = 0.1139);
MVP
0.56
MPC
0.32
ClinPred
0.99
D
GERP RS
5.2
Varity_R
0.48
gMVP
0.74

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.32
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.32
Position offset: 1

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: rs761241421; hg19: chr10-88418336; API