ClinVar Miner

Submissions for variant NM_006346.4(PIBF1):c.1508A>G (p.Tyr503Cys)

gnomAD frequency: 0.00002  dbSNP: rs144610914
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Johns Hopkins Genomics, Johns Hopkins University RCV000735944 SCV001478434 likely pathogenic Joubert syndrome 33 2021-01-18 criteria provided, single submitter clinical testing This PIBF1 variant (rs144610914) is rare (<0.1%) in a large population dataset (gnomAD: 15/273344 total alleles; 0.005%; no homozygotes) and has an entry in ClinVar. It has been reported in a compound heterozygous state with a nonsense variant in a patient with Joubert syndrome. Three bioinformatics tools predict this variant would be damaging The tyrosine residue at this position is strongly conserved across the species assessed. This variant is not predicted to affect normal exon 12 splicing, although this has not been confirmed experimentally to our knowledge. We consider c.1508A>G to be likely pathogenic.
3billion RCV000735944 SCV002521045 likely pathogenic Joubert syndrome 33 2022-05-22 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.006%). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000598934). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
Institute of Human Genetics, Heidelberg University RCV000735944 SCV000863406 pathogenic Joubert syndrome 33 no assertion criteria provided research The variant is observed as compound heterozygous along with the variant at 13:73468052 in the PIBF1 gene.
Dobyns Lab, Seattle Children's Research Institute RCV000779664 SCV000916346 pathogenic Cephalocele; Joubert syndrome 33 2019-02-18 no assertion criteria provided research
University of Washington Center for Mendelian Genomics, University of Washington RCV001257995 SCV001434808 likely pathogenic Dandy-Walker syndrome no assertion criteria provided research
OMIM RCV000735944 SCV001438709 pathogenic Joubert syndrome 33 2020-10-27 no assertion criteria provided literature only

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