ClinVar Miner

Submissions for variant NM_003664.5(AP3B1):c.1412T>A (p.Met471Lys)

gnomAD frequency: 0.00002  dbSNP: rs771964089
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000767892 SCV000898525 uncertain significance Hermansky-Pudlak syndrome 2 2021-03-30 criteria provided, single submitter clinical testing AP3B1 NM_003664.4 exon 14 p.Met471Lys (c.1412T>A): This variant has not been reported in the literature and is present in 0.07% (26/34586) of Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/5-77452143-A-T). Evolutionary conservation and 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000767892 SCV003295549 uncertain significance Hermansky-Pudlak syndrome 2 2022-08-17 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 471 of the AP3B1 protein (p.Met471Lys). This variant is present in population databases (rs771964089, gnomAD 0.08%). 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: 625886). 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.
Ambry Genetics RCV004027206 SCV004905788 uncertain significance Inborn genetic diseases 2024-01-23 criteria provided, single submitter clinical testing The c.1412T>A (p.M471K) alteration is located in exon 14 (coding exon 14) of the AP3B1 gene. This alteration results from a T to A substitution at nucleotide position 1412, causing the methionine (M) at amino acid position 471 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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