Variant rs2675703 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_033282.4(OPN4):c.29C>G(p.Pro10Arg) 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. 15/21 in silico tools predict a benign 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. P10L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

OPN4
NM_033282.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.767

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]

OPN4 links:

ENSG00000289258 (HGNC:):

ENSG00000289258 links:

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=0.1088309).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPN4	NM_033282.4 link	c.29C>G	p.Pro10Arg	missense_variant	Exon 1 of 10	ENST00000241891.10	NP_150598.1	Q9UHM6-1
OPN4	NM_001030015.3 link	c.29C>G	p.Pro10Arg	missense_variant	Exon 1 of 11		NP_001025186.1	Q9UHM6-2
OPN4	XM_017016955.2 link	c.29C>G	p.Pro10Arg	missense_variant	Exon 1 of 10		XP_016872444.1
OPN4	XM_017016956.2 link	c.29C>G	p.Pro10Arg	missense_variant	Exon 1 of 9		XP_016872445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPN4	ENST00000241891.10 link	c.29C>G	p.Pro10Arg	missense_variant	Exon 1 of 10	1	NM_033282.4	ENSP00000241891.5		Q9UHM6-1
ENSG00000289258	ENST00000443292.2 link	c.29C>G	p.Pro10Arg	missense_variant	Exon 1 of 18	1		ENSP00000393132.2		C9JWU6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.18

DANN

Benign

0.72

DEOGEN2

Benign

0.085

.;T;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.46

T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.2

M;M;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.70

N;N;N

REVEL

Benign

0.087

Sift

Benign

0.12

T;T;T

Sift4G

Uncertain

0.029

D;D;D

Polyphen

0.77

P;P;B

Vest4

0.20

MutPred

0.16

Loss of glycosylation at P10 (P = 0.0171);Loss of glycosylation at P10 (P = 0.0171);Loss of glycosylation at P10 (P = 0.0171);

MVP

0.71

MPC

0.064

ClinPred

0.13

GERP RS

-2.1

Varity_R

0.032

gMVP

0.27

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over