Variant X-154153018-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020061.6(OPN1LW):c.488G>T(p.Arg163Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 0)

Consequence

OPN1LW
NM_020061.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:3

Conservation

PhyloP100: 0.0950

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14311004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPN1LW	NM_020061.6 linkuse as main transcript	c.488G>T	p.Arg163Ile	missense_variant	3/6	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.488G>T	p.Arg163Ile	missense_variant	3/6	1	NM_020061.6	ENSP00000358967.4	P04000
OPN1LW	ENST00000442922.1 linkuse as main transcript	c.77G>T	p.Arg26Ile	missense_variant	1/4	5		ENSP00000402493.1	H0Y622
OPN1LW	ENST00000463296.1 linkuse as main transcript	n.498G>T		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.000391

AC:

AN:

168881

Hom.:

AF XY:

0.000123

AC XY:

AN XY:

56791

show subpopulations

Gnomad AFR exome

AF:

0.000155

Gnomad AMR exome

AF:

0.000534

Gnomad ASJ exome

AF:

0.000727

Gnomad EAS exome

AF:

0.000151

Gnomad SAS exome

AF:

0.0000567

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000548

Gnomad OTH exome

AF:

0.000477

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.000547

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000319

AC:

ExAC

AF:

0.000363

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Uncertain significance, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Uncertain significance, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2023

The c.488G>T (p.R163I) alteration is located in exon 3 (coding exon 3) of the OPN1LW gene. This alteration results from a G to T substitution at nucleotide position 488, causing the arginine (R) at amino acid position 163 to be replaced by an isoleucine (I). 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

Uncertain

0.47

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

0.99

FATHMM_MKL

Benign

0.19

LIST_S2

Pathogenic

0.98

.;D

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.94

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-5.2

D;D

REVEL

Benign

0.25

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.031

D;D

Vest4

0.15

MVP

0.62

MPC

2.2

ClinPred

0.12

GERP RS

2.6

gMVP

0.83

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

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