Submissions for variant NM_003664.5(AP3B1):c.1311A>T (p.Glu437Asp)

gnomAD frequency: 0.00001  dbSNP: rs1160297829

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001220032	SCV001392003	uncertain significance	Hermansky-Pudlak syndrome 2	2021-08-27	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid with aspartic acid at codon 437 of the AP3B1 protein (p.Glu437Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with AP3B1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001220032	SCV001468408	uncertain significance	Hermansky-Pudlak syndrome 2	2021-03-30	criteria provided, single submitter	clinical testing	AP3B1 NM_003664.4 exon13 p.Glu437Asp (c.1311A>T): This variant has not been reported in the literature and is not present in large control databases. Evolutionary conservation suggests that this variant may impact the protein; computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.