Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Genomics, |
RCV002208752 | SCV002495809 | uncertain significance | Hermansky-Pudlak syndrome 10 | 2021-04-30 | criteria provided, single submitter | clinical testing | AP3D1 NM_001261826.1 intron 22 c.2601+6G>T:This variant has not been reported in the literature but is present in 0.05% (4/68010) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/19-2114119-C-A?dataset=gnomad_r3). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Although this variant occurs in the splice region, computational prediction tools do not suggest that it alters 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. |
Labcorp Genetics |
RCV003774629 | SCV004683487 | uncertain significance | not provided | 2023-05-12 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1675095). This sequence change falls in intron 22 of the AP3D1 gene. It does not directly change the encoded amino acid sequence of the AP3D1 protein. It affects a nucleotide within the consensus splice site. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with AP3D1-related conditions. 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 is not likely to affect RNA splicing. 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. |