ClinVar Miner

Submissions for variant NM_003664.5(AP3B1):c.2572A>G (p.Ile858Val)

gnomAD frequency: 0.00003  dbSNP: rs150765181
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000215480 SCV000271504 uncertain significance not specified 2015-08-12 criteria provided, single submitter clinical testing The p.Ile858Val variant in AP3B1 has not been previously reported in individuals with pulmonary disease, but has been identified in 3/65412 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSN P rs150765181). Computational prediction tools and conservation analysis do no t provide strong support for or against an impact to the protein. In summary, th e clinical significance of the p.Ile858Val variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV001062212 SCV001226994 uncertain significance Hermansky-Pudlak syndrome 2 2021-09-02 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 858 of the AP3B1 protein (p.Ile858Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs150765181, ExAC 0.005%). This variant has not been reported in the literature in individuals affected with AP3B1-related conditions. ClinVar contains an entry for this variant (Variation ID: 228441). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.

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