Variant X-154154587-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_020061.6(OPN1LW):c.592G>A(p.Gly198Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000838 in 1,073,963 control chromosomes in the GnomAD database, including 1 homozygotes. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000010 ( 0 hom., 0 hem., cov: 16)

Exomes 𝑓: 0.0000084 ( 1 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

OPN1LW
NM_020061.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.65

Variant links:

Genes affected

OPN1LW (HGNC:9936): (opsin 1, long wave sensitive) This gene encodes for a light absorbing visual pigment of the opsin gene family. The encoded protein is called red cone photopigment or long-wavelength sensitive opsin. Opsins are G-protein coupled receptors with seven transmembrane domains, an N-terminal extracellular domain, and a C-terminal cytoplasmic domain. This gene and the medium-wavelength opsin gene are tandemly arrayed on the X chromosome and frequent unequal recombination and gene conversion may occur between these sequences. X chromosomes may have fusions of the medium- and long-wavelength opsin genes or may have more than one copy of these genes. Defects in this gene are the cause of partial, protanopic colorblindness. [provided by RefSeq, Jul 2008]

OPN1LW links:

OPN1LW (HGNC:):

OPN1LW links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.959

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPN1LW	NM_020061.6 linkuse as main transcript	c.592G>A	p.Gly198Ser	missense_variant	4/6	ENST00000369951.9	NP_064445.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OPN1LW	ENST00000369951.9 linkuse as main transcript	c.592G>A	p.Gly198Ser	missense_variant	4/6	1	NM_020061.6	ENSP00000358967.4	P04000
OPN1LW	ENST00000442922.1 linkuse as main transcript	c.181G>A	p.Gly61Ser	missense_variant	2/4	5		ENSP00000402493.1	H0Y622
OPN1LW	ENST00000463296.1 linkuse as main transcript	n.588+1479G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000105

AC:

AN:

95454

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

20938

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000212

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000562

AC:

AN:

178050

Hom.:

AF XY:

0.0000156

AC XY:

AN XY:

64142

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:

0.0000127

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000838

AC:

AN:

1073963

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

343793

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000334

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000251

Gnomad4 NFE exome

AF:

0.00000729

Gnomad4 OTH exome

AF:

0.0000221

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000105

AC:

AN:

95454

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

20938

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000212

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000168

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

Nov 21, 2024

The c.592G>A (p.G198S) alteration is located in exon 4 (coding exon 4) of the OPN1LW gene. This alteration results from a G to A substitution at nucleotide position 592, causing the glycine (G) at amino acid position 198 to be replaced by a serine (S). 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

0.91

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

DANN

Uncertain

1.0

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

.;D

M_CAP

Pathogenic

0.56

MetaRNN

Pathogenic

0.96

D;D

MetaSVM

Uncertain

0.39

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-4.1

D;D

REVEL

Pathogenic

0.81

Sift

Uncertain

0.025

D;D

Sift4G

Uncertain

0.011

D;D

Vest4

0.91

MutPred

0.80

Gain of glycosylation at G198 (P = 0.0478);.;

MVP

0.99

MPC

1.7

ClinPred

0.97

GERP RS

4.3

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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