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

gnomAD frequency: 0.00002  dbSNP: rs144610914

Total submissions: 7

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, Medical Genetics	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.
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV000735944	SCV005200985	likely pathogenic	Joubert syndrome 33	2024-05-02	criteria provided, single submitter	clinical testing	PM1, PM3_Strong, PM2
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