Submissions for variant NM_003664.5(AP3B1):c.2915A>G (p.Asn972Ser)

gnomAD frequency: 0.00213  dbSNP: rs139968311

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000547832	SCV000639574	benign	Hermansky-Pudlak syndrome 2	2024-01-25	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000547832	SCV000898523	uncertain significance	Hermansky-Pudlak syndrome 2	2021-03-30	criteria provided, single submitter	clinical testing	AP3B1 NM_003664.4 exon 25 p.Asn972Ser (c.2915A>G): This variant has not been reported in the literature but is present in 0.6% (163/24026) of African alleles, including 1 homozygote in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs139968311). This variant is present in ClinVar (Variation ID:464884). This variant amino acid Serine (Ser) is present in >40 species and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Illumina Laboratory Services, Illumina	RCV000547832	SCV001318860	likely benign	Hermansky-Pudlak syndrome 2	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Genetic Services Laboratory, University of Chicago	RCV001821544	SCV002069762	likely benign	not specified	2018-05-31	criteria provided, single submitter	clinical testing
GeneDx	RCV002245004	SCV002512944	uncertain significance	not provided	2022-04-11	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002263771	SCV002542923	likely benign	Autoinflammatory syndrome	2020-07-29	criteria provided, single submitter	clinical testing
Genetics and Molecular Pathology, SA Pathology	RCV002466530	SCV002761383	uncertain significance	Hermansky-Pudlak syndrome	2019-10-02	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV002245004	SCV004042225	likely benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	AP3B1: BP4, BS1
PreventionGenetics, part of Exact Sciences	RCV003960313	SCV004772634	likely benign	AP3B1-related disorder	2019-07-31	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).