X-154153044-G-A

Position:

• chrX-154153044-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_020061.6(OPN1LW):​c.514G>A​(p.Gly172Ser) variant causes a missense change. In-silico tool predicts a pathogenic 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: OPN1LW NM_020061.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.68

Genes affected

OPN1LW (HGNC:9936): (opsin 1, long wave sensitive) This gene encodes for a light absorbing visual pigment of the opsin gene family. The encoded protein is called red cone photopigment or long-wavelength sensitive opsin. Opsins are G-protein coupled receptors with seven transmembrane domains, an N-terminal extracellular domain, and a C-terminal cytoplasmic domain. This gene and 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 partial, protanopic colorblindness. [provided by RefSeq, Jul 2008]

OPN1LW (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.801

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPN1LW	NM_020061.6	c.514G>A	p.Gly172Ser	missense_variant	3/6	ENST00000369951.9	NP_064445.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPN1LW	ENST00000369951.9	c.514G>A	p.Gly172Ser	missense_variant	3/6	1	NM_020061.6	ENSP00000358967.4
OPN1LW	ENST00000442922.1	c.103G>A	p.Gly35Ser	missense_variant	1/4	5		ENSP00000402493.1
OPN1LW	ENST00000463296.1	n.524G>A		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.0000178 AC: 3 AN: 168909 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 56807

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: 0.000134

Gnomad NFE exome AF: 0.0000137

Gnomad OTH exome AF: 0.00

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

Dec 06, 2024

The c.514G>A (p.G172S) alteration is located in exon 3 (coding exon 3) of the OPN1LW gene. This alteration results from a G to A substitution at nucleotide position 514, causing the glycine (G) at amino acid position 172 to be replaced by a serine (S). 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
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	1.0
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.99	.;D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Benign	-0.44	T
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0030	D;D
Vest4		0.69
MutPred		0.57		Gain of glycosylation at G172 (P = 0.0308);.;
MVP		0.95
MPC		1.7
ClinPred		0.93	D
GERP RS		3.7
gMVP		0.91

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: rs1557157644; hg19: chrX-153418517;