rs61752894
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000329.3(RPE65):c.644-44_644-43del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 1,138,324 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
RPE65
NM_000329.3 intron
NM_000329.3 intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.212
Genes affected
RPE65 (HGNC:10294): (retinoid isomerohydrolase RPE65) The protein encoded by this gene is a component of the vitamin A visual cycle of the retina which supplies the 11-cis retinal chromophore of the photoreceptors opsin visual pigments. It is a member of the carotenoid cleavage oxygenase superfamily. All members of this superfamily are non-heme iron oxygenases with a seven-bladed propeller fold and oxidatively cleave carotenoid carbon:carbon double bonds. However, the protein encoded by this gene has acquired a divergent function that involves the concerted O-alkyl ester cleavage of its all-trans retinyl ester substrate and all-trans to 11-cis double bond isomerization of the retinyl moiety. As such, it performs the essential enzymatic isomerization step in the synthesis of 11-cis retinal. Mutations in this gene are associated with early-onset severe blinding disorders such as Leber congenital. [provided by RefSeq, Oct 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPE65 | NM_000329.3 | c.644-44_644-43del | intron_variant | ENST00000262340.6 | |||
LOC124904198 | XR_007066164.1 | n.72-8839_72-8838del | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPE65 | ENST00000262340.6 | c.644-44_644-43del | intron_variant | 1 | NM_000329.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 149556Hom.: 0 Cov.: 32 FAILED QC
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GnomAD4 exome AF: 0.0000132 AC: 15AN: 1138324Hom.: 0 AF XY: 0.0000122 AC XY: 7AN XY: 571578
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GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 149556Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 72928
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ClinVar
Not reported inComputational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at