Submissions for variant NM_148919.4(PSMB8):c.22G>A (p.Gly8Arg)

gnomAD frequency: 0.02384  dbSNP: rs114772012

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000272614	SCV000462144	benign	Proteasome-associated autoinflammatory syndrome 1	2018-01-13	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003761941	SCV000640471	benign	Proteosome-associated autoinflammatory syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002261080	SCV002542816	benign	Autoinflammatory syndrome	2022-01-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001572723	SCV003917047	benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	PSMB8: BS1, BS2
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000272614	SCV003920361	likely benign	Proteasome-associated autoinflammatory syndrome 1	2022-08-08	criteria provided, single submitter	clinical testing	PSMB8 NM_148919.3 exon 1 p.Gly8Arg (c.22G>A): This variant has been reported in the literature in at least 1 individual with PASH (Pyoderma Gangrenosum, Acne, and Suppurative Hidradenitis) syndrome (Marzano 2014 PMID:25501066). This variant is present in 4.6% (494/10576) of Finnish alleles, including 5 homozygotes, with similar frequencies across other sub-populations in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/6-32843975-C-T?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:356370). Evolutionary conservation for this variant is limited, though 2 other species (squirrel and squirrel monkey) carry this variant amino acid (Arginine) as their wild type; computational predictive tools suggest that this variant may not impact the protein. In summary, this variant is not expected to cause disease and is classified as benign.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001572723	SCV001797524	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001572723	SCV001930879	likely benign	not provided		no assertion criteria provided	clinical testing