10-86659362-G-T

Variant names:

• chr10-86659362-G-T
• rs143017128
• NM_033282.4:c.694G>T

Variant summary

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

The NM_033282.4(OPN4):​c.694G>T​(p.Val232Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,600 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: OPN4 NM_033282.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.07

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

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
OPN4	NM_033282.4	c.694G>T	p.Val232Leu	missense_variant	Exon 5 of 10	ENST00000241891.10	NP_150598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPN4	ENST00000241891.10	c.694G>T	p.Val232Leu	missense_variant	Exon 5 of 10	1	NM_033282.4	ENSP00000241891.5
ENSG00000289258	ENST00000443292.2	c.727G>T	p.Val243Leu	missense_variant	Exon 6 of 18	1		ENSP00000393132.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461600 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727124

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000899

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	.;T;.
Eigen	Benign	0.17
Eigen_PC	Benign	0.035
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	2.0	.;M;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.22	T;T;T
Polyphen		0.96	D;P;P
Vest4		0.54
MutPred		0.43		Loss of sheet (P = 0.0817);.;Loss of sheet (P = 0.0817);
MVP		0.59
MPC		0.29
ClinPred		0.77	D
GERP RS		3.2
Varity_R		0.11
gMVP		0.71

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: rs143017128; hg19: chr10-88419119;