rs104894912

Variant names:

• chrX-154154734-C-T
• rs104894912
• NM_020061.6:c.739C>T

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_020061.6(OPN1LW):​c.739C>T​(p.Arg247*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 17)
• Consequence: OPN1LW NM_020061.6 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.67

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]

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-154154734-C-T is Pathogenic according to our data. Variant chrX-154154734-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 10503.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-154154734-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPN1LW	NM_020061.6	c.739C>T	p.Arg247*	stop_gained	Exon 4 of 6	ENST00000369951.9	NP_064445.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPN1LW	ENST00000369951.9	c.739C>T	p.Arg247*	stop_gained	Exon 4 of 6	1	NM_020061.6	ENSP00000358967.4
OPN1LW	ENST00000442922.1	c.328C>T	p.Arg110*	stop_gained	Exon 2 of 4	5		ENSP00000402493.1
OPN1LW	ENST00000463296.1	n.589-1560C>T		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes Cov.: 17

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 17

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Cone monochromatism Pathogenic:1

Nov 01, 1993

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.73	D
BayesDel_noAF	Pathogenic	0.62
CADD	Pathogenic	35
DANN	Uncertain	1.0
FATHMM_MKL	Uncertain	0.96	D
Vest4		0.31
GERP RS		4.3
Mutation Taster		=8/192	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs104894912; hg19: chrX-153420209;