X-154225169-T-C

Position:

• chrX-154225169-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001048181.3(OPN1MW2):​c.374T>C​(p.Met125Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 2.05

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPN1MW2	NM_001048181.3	c.374T>C	p.Met125Thr	missense_variant	2/6	ENST00000369929.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPN1MW2	ENST00000369929.8	c.374T>C	p.Met125Thr	missense_variant	2/6	1	NM_001048181.3	P1
OPN1MW2	ENST00000488220.1	n.393T>C		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.0000305 AC: 5 AN: 163685 Hom.: 0 AF XY: 0.0000549 AC XY: 3 AN XY: 54687

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000692

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000166 AC: 1

ExAC AF: 0.0000457 AC: 5

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

Dec 08, 2023

The c.374T>C (p.M125T) alteration is located in exon 2 (coding exon 2) of the OPN1MW2 gene. This alteration results from a T to C substitution at nucleotide position 374, causing the methionine (M) at amino acid position 125 to be replaced by a threonine (T). 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	-0.24	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.013	T
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.0046	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.21	T
Vest4		0.52
MVP		0.55
MPC		2.2
ClinPred		0.087	T
GERP RS		3.0
Varity_R		0.25
gMVP		0.69

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: rs202106144; hg19: chrX-153490638;