X-154230656-G-A

Position:

• chrX-154230656-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001048181.3(OPN1MW2):​c.853G>A​(p.Ala285Thr) 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: OPN1MW2 NM_001048181.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: -0.338

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04442644).
• BP6: Variant X-154230656-G-A is Benign according to our data. Variant chrX-154230656-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1284756.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154230656-G-A is described in Lovd as [Likely_benign]. Variant chrX-154230656-G-A is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPN1MW2	NM_001048181.3	c.853G>A	p.Ala285Thr	missense_variant	5/6	ENST00000369929.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPN1MW2	ENST00000369929.8	c.853G>A	p.Ala285Thr	missense_variant	5/6	1	NM_001048181.3	P1
OPN1MW2	ENST00000430419.1	c.382+58G>A		intron_variant		5
OPN1MW2	ENST00000488220.1			downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.000599 AC: 85 AN: 142010 Hom.: 15 AF XY: 0.000674 AC XY: 29 AN XY: 43030

Gnomad AFR exome AF: 0.000897

Gnomad AMR exome AF: 0.000748

Gnomad ASJ exome AF: 0.000836

Gnomad EAS exome AF: 0.000678

Gnomad SAS exome AF: 0.000224

Gnomad FIN exome AF: 0.000146

Gnomad NFE exome AF: 0.000555

Gnomad OTH exome AF: 0.00166

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.00182 Hom.: 5

ExAC AF: 0.000500 AC: 50

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	OPN1MW2: BP4, BS2; OPN1MW3: BP4, BS2 -

not specified Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.0020
DANN	Benign	0.65
DEOGEN2	Benign	0.082	T
FATHMM_MKL	Benign	0.024	N
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.11
Sift	Benign	1.0	T
Sift4G	Benign	0.19	T
Vest4		0.34
MutPred		0.59		Loss of catalytic residue at A285 (P = 0.0596);
MVP		0.50
MPC		2.0
ClinPred		0.011	T
GERP RS		-3.3
Varity_R		0.053
gMVP		0.18

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: rs1065438; hg19: chrX-153496125; COSMIC: COSV62732860; COSMIC: COSV62732860;