6-47791834-T-C

Position:

• chr6-47791834-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_181744.4(OPN5):​c.283T>C​(p.Phe95Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign 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: 5.58

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]

OPN5 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27811182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPN5	NM_181744.4	c.283T>C	p.Phe95Leu	missense_variant	3/7	ENST00000371211.7	NP_859528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPN5	ENST00000371211.7	c.283T>C	p.Phe95Leu	missense_variant	3/7	1	NM_181744.4	ENSP00000360255.2
OPN5	ENST00000244799.4	n.248T>C		non_coding_transcript_exon_variant	2/7	1
OPN5	ENST00000489301.6	c.283T>C	p.Phe95Leu	missense_variant	3/7	5		ENSP00000426991.1
OPN5	ENST00000393699.2	c.283T>C	p.Phe95Leu	missense_variant	3/6	2		ENSP00000377302.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Dec 27, 2022

The c.283T>C (p.F95L) alteration is located in exon 3 (coding exon 3) of the OPN5 gene. This alteration results from a T to C substitution at nucleotide position 283, causing the phenylalanine (F) at amino acid position 95 to be replaced by a leucine (L). 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	0.92
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.29	.;T;T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	0.073
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.73	T;T;.;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.62	.;N;N;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.9	D;.;D;D
REVEL	Benign	0.14
Sift	Benign	0.29	T;.;T;T
Sift4G	Benign	0.38	T;.;T;T
Polyphen		0.0090	.;B;B;.
Vest4		0.35
MutPred		0.45		Gain of catalytic residue at F95 (P = 0.0551);Gain of catalytic residue at F95 (P = 0.0551);Gain of catalytic residue at F95 (P = 0.0551);Gain of catalytic residue at F95 (P = 0.0551);
MVP		0.34
MPC		0.70
ClinPred		0.82	D
GERP RS		5.1
Varity_R		0.53
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-47759570;