ClinVar Miner

Submissions for variant NM_000329.3(RPE65):c.441A>G (p.Thr147=)

gnomAD frequency: 0.00012  dbSNP: rs185049543
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Leber Congenital Amaurosis/early Onset Retinal Dystrophy Variant Curation Expert Panel, ClinGen RCV004527401 SCV005038770 likely benign RPE65-related recessive retinopathy 2024-04-22 reviewed by expert panel curation NM_000329.3(RPE65):c.441A>C (p.Thr147=) is a synonymous variant located in exon 5. This variant is present in gnomAD v.2.1.1 at a GrpMax allele frequency of 0.006282, with 142 alleles/19954 total alleles in the East Asian population, which is higher than the ClinGen LCA / eoRD VCEP BS1 threshold of >0.0008 (BS1). The splicing impact predictor SpliceAI gives a delta score of 0.05 for donor gain, which is below the ClinGen LCA / eoRD VCEP recommended threshold of <0.1 and does not predict an impact on splicing (BP4, BP7). In summary, this variant meets the criteria to be classified as likely benign for RPE65-related recessive retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen LCA / eoRD VCEP: BS1, BP4, and BP7. (VCEP specifications version 1.0.0; date of approval 09/21/2023).
Labcorp Genetics (formerly Invitae), Labcorp RCV000889235 SCV001032902 benign Leber congenital amaurosis 2; Retinitis pigmentosa 20 2024-01-31 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001102521 SCV001259199 uncertain significance Retinitis pigmentosa 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV001102522 SCV001259200 likely benign Leber congenital amaurosis 2 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Dept Of Ophthalmology, Nagoya University RCV003890018 SCV004706385 likely benign Retinal dystrophy 2023-10-01 criteria provided, single submitter research
Natera, Inc. RCV001275286 SCV001460286 benign Leber congenital amaurosis 2019-11-11 no assertion criteria provided clinical testing

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