Variant 6-47808158-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_181744.4(OPN5):c.761C>T(p.Ala254Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,592 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: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

OPN5
NM_181744.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.29

Variant links:

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 links:

OPN5 (HGNC:):

OPN5 links:

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ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
OPN5	NM_181744.4 linkuse as main transcript	c.761C>T	p.Ala254Val	missense_variant	5/7	ENST00000371211.7	NP_859528.1	Q6U736

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OPN5	ENST00000371211.7 linkuse as main transcript	c.761C>T	p.Ala254Val	missense_variant	5/7	1	NM_181744.4	ENSP00000360255.2	Q6U736
OPN5	ENST00000244799.4 linkuse as main transcript	n.806C>T		non_coding_transcript_exon_variant	5/7	1
OPN5	ENST00000489301.6 linkuse as main transcript	c.761C>T	p.Ala254Val	missense_variant	5/7	5		ENSP00000426991.1	D6RDV4
OPN5	ENST00000393699.2 linkuse as main transcript	c.761C>T	p.Ala254Val	missense_variant	5/6	2		ENSP00000377302.2	J3KPQ2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250942

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135644

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461592

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727094

show subpopulations

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.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.761C>T (p.A254V) alteration is located in exon 5 (coding exon 5) of the OPN5 gene. This alteration results from a C to T substitution at nucleotide position 761, causing the alanine (A) at amino acid position 254 to be replaced by a valine (V). 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

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.28

.;T;T;.

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;.;D

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.72

D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

.;L;L;.

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-2.6

D;.;D;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0030

D;.;D;D

Sift4G

Benign

0.12

T;.;T;T

Polyphen

1.0

.;D;D;.

Vest4

0.83

MutPred

0.52

Gain of catalytic residue at A254 (P = 0.0741);Gain of catalytic residue at A254 (P = 0.0741);Gain of catalytic residue at A254 (P = 0.0741);Gain of catalytic residue at A254 (P = 0.0741);

MVP

0.54

MPC

1.6

ClinPred

0.99

GERP RS

5.7

Varity_R

0.45

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over