X-154227239-A-C

Position:

• chrX-154227239-A-C

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.457A>C​(p.Met153Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/17 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:1
• Conservation: PhyloP100: -2.67

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]

OPN1MW2 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007891893).
• BP6: Variant X-154227239-A-C is Benign according to our data. Variant chrX-154227239-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2345459.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPN1MW2	NM_001048181.3	c.457A>C	p.Met153Leu	missense_variant	3/6	ENST00000369929.8	NP_001041646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPN1MW2	ENST00000369929.8	c.457A>C	p.Met153Leu	missense_variant	3/6	1	NM_001048181.3	ENSP00000358945.4
OPN1MW2	ENST00000430419.1	c.43A>C	p.Met15Leu	missense_variant	1/4	5		ENSP00000403023.1
OPN1MW2	ENST00000488220.1	n.476A>C		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.00392 AC: 144 AN: 36714 Hom.: 4 AF XY: 0.00104 AC XY: 9 AN XY: 8686

Gnomad AFR exome AF: 0.00566

Gnomad AMR exome AF: 0.00461

Gnomad ASJ exome AF: 0.00368

Gnomad EAS exome AF: 0.00133

Gnomad SAS exome AF: 0.00435

Gnomad FIN exome AF: 0.000846

Gnomad NFE exome AF: 0.00413

Gnomad OTH exome AF: 0.00508

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.00706 Hom.: 25

ExAC AF: 0.000486 AC: 13

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.0070
DANN	Benign	0.27
DEOGEN2	Benign	0.0097	T
FATHMM_MKL	Benign	0.033	N
MetaRNN	Benign	0.0079	T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.95	N
REVEL	Benign	0.045
Sift	Benign	0.57	T
Sift4G	Benign	1.0	T
Vest4		0.12
MutPred		0.38		Loss of MoRF binding (P = 0.1842);
MVP		0.17
MPC		1.8
ClinPred		0.0078	T
GERP RS		-5.3
Varity_R		0.15
gMVP		0.50

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: rs782285971; hg19: chrX-153492708;