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NM_000329.3(RPE65):c.399T>C (p.Leu133=) AND RPE65-related recessive retinopathy

Germline classification:
Benign (1 submission)
Last evaluated:
Apr 22, 2024
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV004527313.1

Allele description [Variation Report for NM_000329.3(RPE65):c.399T>C (p.Leu133=)]

NM_000329.3(RPE65):c.399T>C (p.Leu133=)

Gene:
RPE65:retinoid isomerohydrolase RPE65 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p31.3
Genomic location:
Preferred name:
NM_000329.3(RPE65):c.399T>C (p.Leu133=)
Other names:
NM_000329.3(RPE65):c.399T>C; p.Leu133=
HGVS:
  • NC_000001.11:g.68444627A>G
  • NG_008472.2:g.10333T>C
  • NM_000329.3:c.399T>CMANE SELECT
  • NP_000320.1:p.Leu133=
  • NC_000001.10:g.68910310A>G
  • NG_008472.1:g.10333T>C
  • NM_000329.2:c.399T>C
Links:
dbSNP: rs59257923
NCBI 1000 Genomes Browser:
rs59257923
Molecular consequence:
  • NM_000329.3:c.399T>C - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:
RPE65-related recessive retinopathy
Synonyms:
Recessive RPE65 retinopathy
Identifiers:
MONDO: MONDO:0100368; MedGen: CN305526

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005038767ClinGen Leber Congenital Amaurosis/early Onset Retinal Dystrophy Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen LCAeoRD ACMG Specifications RPE65 V1.0.0)		Benign
(Apr 22, 2024) 		germlinecuration

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Leber Congenital Amaurosis/early Onset Retinal Dystrophy Variant Curation Expert Panel, ClinGen, SCV005038767.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

NM_000329.3(RPE65):c.399T>C (p.Leu133=) is a synonymous variant located in exon 5. This variant is present in gnomAD v.4.0.0 at a GrpMax allele frequency of 0.02168, with 1732 alleles/75042 total alleles in the African/African-American population, which is higher than the ClinGen LCA / eoRD VCEP BA1 threshold of >0.008 (BA1). Additionally, there are 20 homozygotes in this population. The splicing impact predictor SpliceAI gives delta scores of 0.07 for acceptor gain and donor gain, which are below the ClinGen LCA / eoRD VCEP recommended threshold of <0.1 and do not predict an impact on splicing (BP4, BP7). In summary, this variant meets the criteria to be classified as benign for RPE65-related recessive retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen LCA / eoRD VCEP: BA1, BP4, and BP7. (VCEP specifications version 1.0.0; date of approval 09/21/2023).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024