Submissions for variant NM_000277.3(PAH):c.1065+3A>G

dbSNP: rs62508689

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen PAH Variant Curation Expert Panel	RCV000758111	SCV000886585	likely pathogenic	Phenylketonuria	2018-12-10	reviewed by expert panel	curation	The c.1065+3A>G variant in PAH was detected in 2 siblings with an increased serum Phenylalanine level of 365 uM. BH4 deficiency was not assessed/reported. (PMID: 8088845) They were compound heterozygous for Y414C. The c.1065+3A>G variant is absent from ExAC, gnomAD, 1000G, and ESP. A deleterious effect is predicted for this variant in HSF and MaxEnt (Alteration of the WT donor site; activation of an intronic cryptic donor site). In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM3, PP1, PP3, PP4.
Eurofins Ntd Llc (ga)	RCV000088736	SCV000331037	uncertain significance	not provided	2015-09-29	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000088736	SCV000889560	uncertain significance	not provided	2018-01-14	criteria provided, single submitter	clinical testing
OMIM	RCV000000665	SCV000020815	pathogenic	Hyperphenylalaninemia	1994-05-15	no assertion criteria provided	literature only
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	RCV000088736	SCV000119318	not provided	not provided		no assertion provided	not provided