ClinVar Miner

Submissions for variant NM_003664.5(AP3B1):c.1363G>A (p.Glu455Lys)

gnomAD frequency: 0.00001  dbSNP: rs1204234337
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000792683 SCV000931993 uncertain significance Hermansky-Pudlak syndrome 2 2024-10-16 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 455 of the AP3B1 protein (p.Glu455Lys). This variant also falls at the last nucleotide of exon 13, which is part of the consensus splice site for this exon. This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 639784). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus 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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