X-154224988-A-G

Position:

• chrX-154224988-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001048181.3(OPN1MW2):​c.193A>G​(p.Ile65Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I65T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 0)
• Consequence: OPN1MW2 NM_001048181.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.54

Genes affected

OPN1MW2 (HGNC:26952): (opsin 1, medium wave sensitive 2) 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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.040789664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPN1MW2	NM_001048181.3	c.193A>G	p.Ile65Val	missense_variant	2/6	ENST00000369929.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPN1MW2	ENST00000369929.8	c.193A>G	p.Ile65Val	missense_variant	2/6	1	NM_001048181.3	P1
OPN1MW2	ENST00000488220.1	n.212A>G		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.000136 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 11, 2022

The c.193A>G (p.I65V) alteration is located in exon 2 (coding exon 2) of the OPN1MW2 gene. This alteration results from a A to G substitution at nucleotide position 193, causing the isoleucine (I) at amino acid position 65 to be replaced by a valine (V). 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
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0020
DANN	Benign	0.19
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.030	N
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.99	N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.028
Sift	Benign	1.0	T
Sift4G	Benign	0.55	T
Vest4		0.035
MutPred		0.39		Gain of catalytic residue at I65 (P = 0.0645);
MVP		0.068
MPC		1.7
ClinPred		0.022	T
GERP RS		0.21
Varity_R		0.025
gMVP		0.28

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

Other links and lift over

dbSNP: rs1557161004; hg19: chrX-153490457;