ClinVar Miner

Submissions for variant NM_003664.5(AP3B1):c.3254G>A (p.Arg1085Gln)

gnomAD frequency: 0.00004  dbSNP: rs151028592
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001222793 SCV001394909 uncertain significance Hermansky-Pudlak syndrome 2 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1085 of the AP3B1 protein (p.Arg1085Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs151028592, ExAC 0.009%). 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. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV001222793 SCV002495790 uncertain significance Hermansky-Pudlak syndrome 2 2022-01-28 criteria provided, single submitter clinical testing This variant has not been reported in the literature but is present in 0.007% (3/41434) African/African American alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/5-78002933-C-T?dataset=gnomad_r3). It is also present in ClinVar (Variation ID:950967). This variant amino acid Glutamine (Gln) is present in multiple evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. Of note, splice prediction tools suggest that this variant may affect splicing. However, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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