chrX-154225126-G-A

Position:

• chrX-154225126-G-A

Variant summary

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

The NM_001048181.3(OPN1MW2):​c.331G>A​(p.Val111Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: OPN1MW2 NM_001048181.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.705

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=0.016506642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPN1MW2	NM_001048181.3	c.331G>A	p.Val111Ile	missense_variant	2/6	ENST00000369929.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPN1MW2	ENST00000369929.8	c.331G>A	p.Val111Ile	missense_variant	2/6	1	NM_001048181.3	P1
OPN1MW2	ENST00000488220.1	n.350G>A		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.00112 AC: 170 AN: 151519 Hom.: 1 AF XY: 0.0000415 AC XY: 2 AN XY: 48187

Gnomad AFR exome AF: 0.000574

Gnomad AMR exome AF: 0.000734

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000878

Gnomad SAS exome AF: 0.00119

Gnomad FIN exome AF: 0.000931

Gnomad NFE exome AF: 0.00161

Gnomad OTH exome AF: 0.00184

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.00439 Hom.: 0

ExAC AF: 0.00184 AC: 200

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

Nov 03, 2023

The c.331G>A (p.V111I) alteration is located in exon 2 (coding exon 2) of the OPN1MW2 gene. This alteration results from a G to A substitution at nucleotide position 331, causing the valine (V) at amino acid position 111 to be replaced by an isoleucine (I). 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	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.8
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0060	T
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.53	N
REVEL	Benign	0.071
Sift	Benign	0.054	T
Sift4G	Benign	0.36	T
Vest4		0.043
MVP		0.39
MPC		1.7
ClinPred		0.021	T
GERP RS		3.0
Varity_R		0.15
gMVP		0.42

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: rs201210169; hg19: chrX-153490595;