Submissions for variant NM_001253852.3(AP4B1):c.616C>T (p.Arg206Ter)

dbSNP: rs762612591

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002539788	SCV003034100	pathogenic	Hereditary spastic paraplegia 47	2024-03-06	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg206*) in the AP4B1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AP4B1 are known to be pathogenic (PMID: 22290197, 24700674, 24781758). This variant is present in population databases (rs762612591, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with AP4B1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1299776). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV001730199	SCV005848373	likely pathogenic	not provided	2024-08-09	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001730199	SCV001977713	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001730199	SCV001979632	pathogenic	not provided		no assertion criteria provided	clinical testing