rs104894915

Variant names:

• chrX-154187939-C-A
• rs104894915
• NM_000513.2:c.282C>A
• OPN1MW p.Asn94Lys

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PP3_Strong PP5

The NM_000513.2(OPN1MW):​c.282C>A​(p.Asn94Lys) variant causes a missense change involving the alteration of a non-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: 2)
• Consequence: OPN1MW NM_000513.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.92
• Publications: 6 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: Ambry Genetics, G2P, Orphanet
• 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 5 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.97
• PP5: Variant X-154187939-C-A is Pathogenic according to our data. Variant chrX-154187939-C-A is described in ClinVar as Pathogenic. ClinVar VariationId is 10512.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.282C>A	p.Asn94Lys	missense	Exon 2 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.282C>A	p.Asn94Lys	missense	Exon 2 of 6	ENSP00000472316.1	P04001
	OPN1MW	ENST00000595330.1	TSL:5	n.292C>A		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 2

GnomAD4 exome Cov.: 8

GnomAD4 genome Cov.: 2

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
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	D
FATHMM_MKL	Uncertain	0.85	D
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.97	D
MetaSVM	Benign	-0.56	T
PhyloP100		1.9
PrimateAI	Pathogenic	0.84	D
Sift4G	Pathogenic	0.0	D
Varity_R		0.93
gMVP		0.98

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: rs104894915;

hg19: chrX-153453428;