rs2675703

chr10-86654812-C-Gchr10-86654812-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 14/20 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767

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]

ACMG classification

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/exons	MANE	UniProt
OPN4	NM_033282.4	c.29C>G	p.Pro10Arg	missense_variant	1/10	ENST00000241891.10
OPN4	NM_001030015.3	c.29C>G	p.Pro10Arg	missense_variant	1/11
OPN4	XM_017016955.2	c.29C>G	p.Pro10Arg	missense_variant	1/10
OPN4	XM_017016956.2	c.29C>G	p.Pro10Arg	missense_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPN4	ENST00000241891.10	c.29C>G	p.Pro10Arg	missense_variant	1/10	1	NM_033282.4	P1
OPN4	ENST00000372071.7	c.29C>G	p.Pro10Arg	missense_variant	1/11	1
OPN4	ENST00000690949.1	n.145+150C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	0.18
Dann	Benign	0.72
Eigen	Benign	-0.86
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.46	T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.2	M;M;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.33	T
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	T
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

Other links and lift over

dbSNP: rs2675703; hg19: chr10-88414569;