X-154195969-G-C

Position:

• chrX-154195969-G-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_000513.2(OPN1MW):​c.1024G>C​(p.Asp342His) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: OPN1MW NM_000513.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.64

Genes affected

OPN1MW (HGNC:4206): (opsin 1, medium wave sensitive) 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.33738905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPN1MW	NM_000513.2	c.1024G>C	p.Asp342His	missense_variant	6/6	ENST00000595290.6	NP_000504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPN1MW	ENST00000595290.6	c.1024G>C	p.Asp342His	missense_variant	6/6	1	NM_000513.2	ENSP00000472316.1
OPN1MW	ENST00000596998.2	c.421G>C	p.Asp141His	missense_variant	4/4	5		ENSP00000469055.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 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

Nov 09, 2024

The c.1024G>C (p.D342H) alteration is located in exon 6 (coding exon 6) of the OPN1MW gene. This alteration results from a G to C substitution at nucleotide position 1024, causing the aspartic acid (D) at amino acid position 342 to be replaced by a histidine (H). 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	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.065	T
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.36	T
PrimateAI	Uncertain	0.61	T
Sift4G	Benign	0.063	T
Polyphen		1.0	D
Vest4		0.30
MutPred		0.35		Loss of ubiquitination at K340 (P = 0.0718);
MVP		0.63
ClinPred		0.99	D
GERP RS		2.7
Varity_R		0.35
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-153461460;