ClinVar Miner

Submissions for variant NM_003664.5(AP3B1):c.1946G>A (p.Arg649Gln)

gnomAD frequency: 0.00001  dbSNP: rs748191084
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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 RCV001216593 SCV001388397 uncertain significance Hermansky-Pudlak syndrome 2 2019-05-06 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with AP3B1-related conditions. This variant is present in population databases (rs748191084, ExAC 0.01%). This sequence change replaces arginine with glutamine at codon 649 of the AP3B1 protein (p.Arg649Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine.
Ambry Genetics RCV002562414 SCV003600384 uncertain significance Inborn genetic diseases 2022-03-02 criteria provided, single submitter clinical testing The c.1946G>A (p.R649Q) alteration is located in exon 17 (coding exon 17) of the AP3B1 gene. This alteration results from a G to A substitution at nucleotide position 1946, causing the arginine (R) at amino acid position 649 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV001216593 SCV005689002 uncertain significance Hermansky-Pudlak syndrome 2 2024-09-19 criteria provided, single submitter clinical testing The AP3B1 c.1946G>A (p.Arg649Gln) change has a maximum subpopulation frequency of 0.0062% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with Hermansky-Pudlak syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.

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