Submissions for variant NM_080632.3(UPF3B):c.697_698del (p.Arg233fs)

dbSNP: rs1064794254

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000483091	SCV000568491	pathogenic	not provided	2019-08-15	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 22609145)
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678370	SCV000804436	pathogenic	Syndromic X-linked intellectual disability 14	2017-03-28	criteria provided, single submitter	provider interpretation	This 2 year old male with global developmental delays, autism spectrum disorder, large stature, and macrocephaly was found to carry a maternally inherited frameshift variant in the UPF3B gene. The patient also has dolicocephaly, wide nasal bridge, epicanthal folds, full lips, and a wide mouth. The patient's mother is unaffected. The patient's maternal great-uncle was found to harbor the same variant; he has an intellectual disability and reported macrocephaly. The c.697_698delAG variant in the UPF3B gene has been reported previously in two brothers, both with developmental delay and renal dysplasia, and one also with macrocephaly (Lynch et al., 2012). The c.697_698delAG variant causes a frameshift and is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is absent from population databases.