NM_020061.6:c.1013G>A

Variant names:

• chrX-154158844-G-A
• rs104894913
• NM_020061.6:c.1013G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PP3_Moderate PP5

The NM_020061.6(OPN1LW):​c.1013G>A​(p.Gly338Glu) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 0)
• Consequence: OPN1LW NM_020061.6 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.46
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• blue cone monochromacy

  Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• red color blindness

  Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.855
• PP5: Variant X-154158844-G-A is Pathogenic according to our data. Variant chrX-154158844-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 10506.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020061.6. 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
	OPN1LW	NM_020061.6	MANE Select	c.1013G>A	p.Gly338Glu	missense	Exon 6 of 6	NP_064445.2	P04000

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPN1LW	ENST00000369951.9	TSL:1 MANE Select	c.1013G>A	p.Gly338Glu	missense	Exon 6 of 6	ENSP00000358967.4	P04000
	OPN1LW	ENST00000442922.1	TSL:5	c.413G>A	p.Gly138Glu	missense	Exon 4 of 4	ENSP00000402493.1	H0Y622

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Protan defect (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
PhyloP100		8.5
gMVP		0.61
Mutation Taster		=26/74	disease causing (ClinVar)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs104894913; hg19: chrX-153424319;