ClinVar Miner

Submissions for variant NM_001261826.3(AP3D1):c.3148G>A (p.Val1050Ile)

gnomAD frequency: 0.00003  dbSNP: rs755674952
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001873993 SCV002118194 uncertain significance not provided 2025-01-01 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1050 of the AP3D1 protein (p.Val1050Ile). 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. ClinVar contains an entry for this variant (Variation ID: 1353985). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Neuberg Centre For Genomic Medicine, NCGM RCV004584927 SCV005073861 uncertain significance Hermansky-Pudlak syndrome 10 criteria provided, single submitter clinical testing The observed missense variant c.3148G>A (p.Val1050Ile) in AP3D1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Val1050Ile variant has allele frequency 0.002% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Uncertain Significance. The amino acid change p.Val1050Ile in AP3D1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Val at position 1050 is changed to a Ile changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS).
Ambry Genetics RCV004953160 SCV005457599 uncertain significance Inborn genetic diseases 2024-09-10 criteria provided, single submitter clinical testing The c.2962G>A (p.V988I) alteration is located in exon 25 (coding exon 25) of the AP3D1 gene. This alteration results from a G to A substitution at nucleotide position 2962, causing the valine (V) at amino acid position 988 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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