X-154154575-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020061.6(OPN1LW):c.580T>C(p.Tyr194His) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 16)
• Consequence: OPN1LW NM_020061.6 missense, splice_region
• Scores: Splicing: ADA: 0.07981
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.91

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.905

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPN1LW	NM_020061.6	c.580T>C	p.Tyr194His	missense_variant, splice_region_variant	4/6	ENST00000369951.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPN1LW	ENST00000369951.9	c.580T>C	p.Tyr194His	missense_variant, splice_region_variant	4/6	1	NM_020061.6	P1
OPN1LW	ENST00000442922.1	c.169T>C	p.Tyr57His	missense_variant, splice_region_variant	2/4	5
OPN1LW	ENST00000463296.1	n.588+1467T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 16

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

Feb 06, 2024

The c.580T>C (p.Y194H) alteration is located in exon 4 (coding exon 4) of the OPN1LW gene. This alteration results from a T to C substitution at nucleotide position 580, causing the tyrosine (Y) at amino acid position 194 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
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.33
Cadd	Pathogenic	26
Dann	Uncertain	1.0
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Pathogenic	0.49	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Uncertain	0.52	D
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Pathogenic	0.81
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Vest4		0.78
MutPred		0.70		Gain of disorder (P = 0.0264);.;
MVP		0.99
MPC		1.9
ClinPred		1.0	D
GERP RS		4.3
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.080
dbscSNV1_RF	Benign	0.31
SpliceAI score (max)		0.020		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-153420050;