ClinVar Miner

Submissions for variant NM_000047.3(ARSL):c.24-1G>A

gnomAD frequency: 0.00001  dbSNP: rs762627146
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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 RCV002240072 SCV002511350 likely pathogenic Chondrodysplasia punctata, brachytelephalangic, autosomal 2023-12-12 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 2 of the ARSE gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ARSE are known to be pathogenic (PMID: 9497243, 23470839). This variant is present in population databases (rs762627146, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with ARSE-related conditions. ClinVar contains an entry for this variant (Variation ID: 1683210). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
3billion, Medical Genetics RCV003152790 SCV003841303 pathogenic X-linked chondrodysplasia punctata 1 2023-02-23 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). This variant was predicted to alter splicing and result in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. The variant has been reported to be associated with ARSL related disorder (ClinVar ID: VCV001683210). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
GeneDx RCV003324850 SCV004030817 uncertain significance not provided 2023-02-22 criteria provided, single submitter clinical testing Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge

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