chr6-47786593-T-C

Position:

• chr6-47786593-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_181744.4(OPN5):​c.209T>C​(p.Ile70Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OPN5 NM_181744.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.17

Genes affected

OPN5 (HGNC:19992): (opsin 5) Opsins are members of the guanine nucleotide-binding protein (G protein)-coupled receptor superfamily. This opsin gene is expressed in the eye, brain, testes, and spinal cord. This gene belongs to the seven-exon subfamily of mammalian opsin genes that includes peropsin (RRH) and retinal G protein coupled receptor (RGR). Like these other seven-exon opsin genes, this family member may encode a protein with photoisomerase activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.907

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPN5	NM_181744.4	c.209T>C	p.Ile70Thr	missense_variant	2/7	ENST00000371211.7	NP_859528.1
OPN5	XM_017010416.2	c.209T>C	p.Ile70Thr	missense_variant	2/8		XP_016865905.1
OPN5	XM_017010410.2	c.41T>C	p.Ile14Thr	missense_variant	1/8		XP_016865899.1
OPN5	XM_017010411.2	c.41T>C	p.Ile14Thr	missense_variant	1/6		XP_016865900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPN5	ENST00000371211.7	c.209T>C	p.Ile70Thr	missense_variant	2/7	1	NM_181744.4	ENSP00000360255.2
OPN5	ENST00000489301.6	c.209T>C	p.Ile70Thr	missense_variant	2/7	5		ENSP00000426991.1
OPN5	ENST00000393699.2	c.209T>C	p.Ile70Thr	missense_variant	2/6	2		ENSP00000377302.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 20, 2023

The c.209T>C (p.I70T) alteration is located in exon 2 (coding exon 2) of the OPN5 gene. This alteration results from a T to C substitution at nucleotide position 209, causing the isoleucine (I) at amino acid position 70 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	.;T;T;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;.;D
M_CAP	Benign	0.040	D
MetaRNN	Pathogenic	0.91	D;D;D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.6	.;L;L;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.7	D;.;D;D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0050	D;.;D;D
Sift4G	Uncertain	0.013	D;.;D;D
Polyphen		0.85	.;P;P;.
Vest4		0.78
MutPred		0.81		Gain of disorder (P = 0.0218);Gain of disorder (P = 0.0218);Gain of disorder (P = 0.0218);Gain of disorder (P = 0.0218);
MVP		0.67
MPC		1.3
ClinPred		0.97	D
GERP RS		5.9
Varity_R		0.34
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-47754329;