Genetic Variant OPN3:p.Gly281Ala (chr1-241597849-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_014322.3(OPN3):c.842G>C(p.Gly281Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OPN3
NM_014322.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.31

Publications

0 publications found

Variant links:

Genes affected

OPN3 (HGNC:14007): (opsin 3) Opsins are members of the guanine nucleotide-binding protein (G protein)-coupled receptor superfamily. In addition to the visual opsins, mammals possess several photoreceptive non-visual opsins that are expressed in extraocular tissues. This gene, opsin 3, is strongly expressed in brain and testis and weakly expressed in liver, placenta, heart, lung, skeletal muscle, kidney, and pancreas. The gene may also be expressed in the retina. The protein has the canonical features of a photoreceptive opsin protein. [provided by RefSeq, Jul 2008]

OPN3 links:

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ACMG classification

Classification was made for transcript

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, 0.878

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014322.3. 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
	OPN3	NM_014322.3	MANE Select	c.842G>C	p.Gly281Ala	missense	Exon 3 of 4	NP_055137.2	Q9H1Y3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OPN3	ENST00000366554.3	TSL:1 MANE Select	c.842G>C	p.Gly281Ala	missense	Exon 3 of 4	ENSP00000355512.2	Q9H1Y3-1
OPN3	ENST00000469376.5	TSL:1	n.*112G>C		non_coding_transcript_exon	Exon 3 of 4	ENSP00000490012.1	Q6P5W7
OPN3	ENST00000490673.5	TSL:1	n.*93G>C		non_coding_transcript_exon	Exon 2 of 3	ENSP00000490178.1	Q6GMT1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151764

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461786

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727190

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111966

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151764

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74102

show subpopulations

African (AFR)

AF:

0.0000485

AC:

AN:

41260

American (AMR)

AF:

0.00

AC:

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67964

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.00089

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

Eigen

Benign

0.16

Eigen_PC

Benign

-0.027

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.68

M_CAP

Benign

0.076

MetaRNN

Pathogenic

0.88

MetaSVM

Uncertain

-0.25

MutationAssessor

Uncertain

2.3

PhyloP100

4.3

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-5.5

REVEL

Uncertain

0.40

Sift

Uncertain

0.013

Sift4G

Uncertain

0.013

Polyphen

1.0

Vest4

0.77

MutPred

0.60

Loss of stability (P = 0.0668)

MVP

0.70

MPC

1.2

ClinPred

0.99

GERP RS

2.1

Varity_R

0.54

gMVP

0.62

Mutation Taster

=54/46

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over