Submissions for variant NM_000047.3(ARSL):c.1743G>A (p.Trp581Ter)

gnomAD frequency: 0.00003  dbSNP: rs80338714

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000485780	SCV000564593	pathogenic	not provided	2023-07-02	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation as the last 9 amino acids are lost, although loss-of-function variants have not been reported downstream of this position in the protein; This variant is associated with the following publications: (PMID: 9863597, 12567415, 26526591, 19839041, 30084160, 32860008, 34529350)
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001196991	SCV001367626	likely pathogenic	See cases	2020-02-18	criteria provided, single submitter	clinical testing	This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2.
Centogene AG - the Rare Disease Company	RCV000012285	SCV001426469	pathogenic	X-linked chondrodysplasia punctata 1		criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000012285	SCV002018874	likely pathogenic	X-linked chondrodysplasia punctata 1	2023-05-30	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000012285	SCV002587080	likely pathogenic	X-linked chondrodysplasia punctata 1	2022-10-07	criteria provided, single submitter	clinical testing	Criteria applied: PVS1_MOD, PS4, PM2_SUP
Invitae	RCV002512981	SCV003516459	pathogenic	Chondrodysplasia punctata, brachytelephalangic, autosomal	2024-01-03	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp581*) in the ARSE gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 9 amino acid(s) of the ARSE protein. This variant is present in population databases (rs80338714, gnomAD 0.002%). This premature translational stop signal has been observed in individuals with chondrodysplasia punctata (PMID: 9863597, 12567415). ClinVar contains an entry for this variant (Variation ID: 11529). For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000012285	SCV004171252	pathogenic	X-linked chondrodysplasia punctata 1	2023-11-30	criteria provided, single submitter	clinical testing
OMIM	RCV000012285	SCV000032519	pathogenic	X-linked chondrodysplasia punctata 1	2003-03-01	no assertion criteria provided	literature only
GeneReviews	RCV000012285	SCV000040399	not provided	X-linked chondrodysplasia punctata 1		no assertion provided	literature only
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV000012285	SCV001190738	pathogenic	X-linked chondrodysplasia punctata 1	2020-02-05	no assertion criteria provided	clinical testing