Variant X-154154725-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_020061.6(OPN1LW):c.730C>G(p.Leu244Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000095 ( 0 hom., 0 hem., cov: 17)

Exomes 𝑓: 0.0000037 ( 1 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

OPN1LW
NM_020061.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.317

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_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26408952).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPN1LW	NM_020061.6 linkuse as main transcript	c.730C>G	p.Leu244Val	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.730C>G	p.Leu244Val	missense_variant	4/6	1	NM_020061.6	ENSP00000358967.4	P04000
OPN1LW	ENST00000442922.1 linkuse as main transcript	c.319C>G	p.Leu107Val	missense_variant	2/4	5		ENSP00000402493.1	H0Y622
OPN1LW	ENST00000463296.1 linkuse as main transcript	n.589-1569C>G		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00000953

AC:

AN:

104919

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

28209

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:

0.0000196

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000369

AC:

AN:

1083344

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

350036

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:

0.00000481

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000953

AC:

AN:

104919

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

28209

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:

0.0000196

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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 13, 2024

The c.730C>G (p.L244V) alteration is located in exon 4 (coding exon 4) of the OPN1LW gene. This alteration results from a C to G substitution at nucleotide position 730, causing the leucine (L) at amino acid position 244 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

Benign

0.11

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.91

.;D

M_CAP

Benign

0.042

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.79

N;N

REVEL

Benign

0.13

Sift

Uncertain

0.0020

D;D

Sift4G

Benign

0.47

T;T

Vest4

0.24

MutPred

0.41

Gain of MoRF binding (P = 0.0861);.;

MVP

0.61

MPC

1.3

ClinPred

0.87

GERP RS

3.4

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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