OPN4 p.Ser131Arg

Variant names:

• chr10-86658132-A-C
• NM_033282.4:c.391A>C
• OPN4 p.Ser131Arg

Your query was ambiguous. Multiple possible variants found:

• chr10-86658132-A-C
• chr10-86658134-C-A
• chr10-86658134-C-G
• chr10-86658132-AGC-CGT
• chr10-86658132-AGC-CGA
• chr10-86658132-AGC-CGG

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_033282.4(OPN4):​c.391A>C​(p.Ser131Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OPN4 NM_033282.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.37
• Publications: 0 publications found

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]

ENSG00000289258 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.857

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033282.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPN4	NM_033282.4	MANE Select	c.391A>C	p.Ser131Arg	missense	Exon 3 of 10	NP_150598.1	Q9UHM6-1
	OPN4	NM_001030015.3		c.424A>C	p.Ser142Arg	missense	Exon 4 of 11	NP_001025186.1	Q9UHM6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPN4	ENST00000241891.10	TSL:1 MANE Select	c.391A>C	p.Ser131Arg	missense	Exon 3 of 10	ENSP00000241891.5	Q9UHM6-1
	ENSG00000289258	ENST00000443292.2	TSL:1	c.424A>C	p.Ser142Arg	missense	Exon 4 of 18	ENSP00000393132.2	C9JWU6
	OPN4	ENST00000372071.7	TSL:1	c.424A>C	p.Ser142Arg	missense	Exon 4 of 11	ENSP00000361141.2	Q9UHM6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		7.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.031	D
Varity_R		0.76
gMVP		0.67
Mutation Taster		=34/66	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-88417889;