rs761241421

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033282.4(OPN4):​c.520C>A​(p.Arg174Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,856 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. R174C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OPN4
NM_033282.4 missense

Scores

10
9

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 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
OPN4NM_033282.4 linkc.520C>A p.Arg174Ser 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>A p.Arg174Ser missense_variant Exon 4 of 10 1 NM_033282.4 ENSP00000241891.5 Q9UHM6-1
ENSG00000289258ENST00000443292.2 linkc.553C>A p.Arg185Ser missense_variant Exon 5 of 18 1 ENSP00000393132.2 C9JWU6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251438
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135906
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:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461856
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727228
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.31
BayesDel_addAF
Benign
0.0063
T
BayesDel_noAF
Benign
-0.13
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.37
.;T;.
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Benign
0.063
D
MetaRNN
Uncertain
0.69
D;D;D
MetaSVM
Benign
-0.70
T
MutationAssessor
Uncertain
2.2
.;M;.
PrimateAI
Benign
0.27
T
PROVEAN
Uncertain
-3.9
D;D;D
REVEL
Benign
0.28
Sift
Uncertain
0.0030
D;D;D
Sift4G
Uncertain
0.0060
D;D;D
Polyphen
0.93
P;P;P
Vest4
0.73
MutPred
0.72
Gain of glycosylation at R185 (P = 0.0595);.;Gain of glycosylation at R185 (P = 0.0595);
MVP
0.54
MPC
0.29
ClinPred
0.98
D
GERP RS
5.2
Varity_R
0.50
gMVP
0.74

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs761241421; hg19: chr10-88418336; API