Variants in ALG3 were first reported in individuals with an autosomal recessive ALG3-related congenital disorder of glycosylation (CDG) in 2004 (Denecke et al., PMID: 15108280). Phenotypes commonly reported with ALG3 variants include severe neurological involvement, craniofacial abnormalities, facial dysmorphism, skeletal anomalies, ophthalmologic impairment, and feeding problems.
Eight variants (missense, nonsense, frameshift), reported in seven probands, in six publications (PMIDs: 33583022, 34090370, 15108280, 31067009, 32389449, 27172925) are included in this curation. The variant p.Gly55= is recurrent and has been included four times within this curation. Most probands were first identified by a CDG type I N-glycosylation defect as determined by a serum isoelectric focusing assay. More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached.
The mechanism of pathogenicity is reported as loss-of-function. Experimental evidence is inconclusive and has not been curated as “definitive” evidence level has been reached based on genetic evidence alone.
In summary, there is definitive evidence to support the relationship between ALG3 and ALG3-related CDG. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on December 6, 2022 (SOP Version 9).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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