X-154195934-G-A

Variant names:

• chrX-154195934-G-A
• rs104894916
• NM_000513.2:c.989G>A

Variant summary

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

The NM_000513.2(OPN1MW):​c.989G>A​(p.Arg330Gln) variant causes a missense change. 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: OPN1MW NM_000513.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.31
• Publications: 5 publications found

Genes affected

OPN1MW (HGNC:4206): (opsin 1, medium wave sensitive) This gene encodes for a light absorbing visual pigment of the opsin gene family. The encoded protein is called green cone photopigment or medium-wavelength sensitive opsin. Opsins are G-protein coupled receptors with seven transmembrane domains, an N-terminal extracellular domain, and a C-terminal cytoplasmic domain. The long-wavelength opsin gene and multiple copies of 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 deutanopic colorblindness. [provided by RefSeq, Mar 2009]

OPN1MW Gene-Disease associations (from GenCC):

• blue cone monochromacy

  Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE, NO_KNOWN Submitted by: Orphanet, G2P, Ambry Genetics
• red-green 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, 0.866
• PP5: Variant X-154195934-G-A is Pathogenic according to our data. Variant chrX-154195934-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 10509.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000513.2. 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
	OPN1MW	NM_000513.2	MANE Select	c.989G>A	p.Arg330Gln	missense	Exon 6 of 6	NP_000504.1	P04001

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPN1MW	ENST00000595290.6	TSL:1 MANE Select	c.989G>A	p.Arg330Gln	missense	Exon 6 of 6	ENSP00000472316.1	P04001
	OPN1MW	ENST00000596998.2	TSL:5	c.386G>A	p.Arg129Gln	missense	Exon 4 of 4	ENSP00000469055.1	H0Y642

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.00 AC: 0 AN: 6

Gnomad NFE exome AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Deuteranomaly (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.3
Varity_R		0.17
gMVP		0.77

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

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

Other links and lift over

dbSNP: rs104894916; hg19: chrX-153461425;