chrX-154154602-T-C
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_020061.6(OPN1LW):c.607T>C(p.Cys203Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000929 in 1,076,532 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Genomes: not found (cov: 16)
Exomes 𝑓: 9.3e-7 ( 0 hom. 0 hem. )
Consequence
OPN1LW
NM_020061.6 missense
NM_020061.6 missense
Scores
11
2
1
Clinical Significance
Conservation
PhyloP100: 7.82
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 14 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.993
PP5
?
Variant X-154154602-T-C is Pathogenic according to our data. Variant chrX-154154602-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 10505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-154154602-T-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OPN1LW | NM_020061.6 | c.607T>C | p.Cys203Arg | missense_variant | 4/6 | ENST00000369951.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OPN1LW | ENST00000369951.9 | c.607T>C | p.Cys203Arg | missense_variant | 4/6 | 1 | NM_020061.6 | P1 | |
OPN1LW | ENST00000442922.1 | c.196T>C | p.Cys66Arg | missense_variant | 2/4 | 5 | |||
OPN1LW | ENST00000463296.1 | n.588+1494T>C | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 16
GnomAD3 genomes
?
Cov.:
16
GnomAD4 exome AF: 9.29e-7 AC: 1AN: 1076532Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 345470
GnomAD4 exome
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1
AN:
1076532
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28
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0
AN XY:
345470
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GnomAD4 genome ? Cov.: 16
GnomAD4 genome
?
Cov.:
16
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jul 19, 2019 | One of the most common pathogenic variants associated with blue cone monochromacy (Buena-Atienza et al., 2016); Functional studies demonstrate loss of cone opsin function with misfolded opsins that are retained in the endoplasmic reticulum and degraded (Kazmi et al., 1997); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 27274860, 22998501, 23139274, 23322568, 25168334, 2788922, 8666378, 27447086, 15094734, 9152227, 30516820, 27339364) - |
Cone monochromatism Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2005 | - - |
Protan defect Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Genetics and Molecular Pathology, SA Pathology | Oct 21, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
A
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Vest4
MutPred
Gain of disorder (P = 0.003);.;
MVP
MPC
ClinPred
D
GERP RS
gMVP
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at