Submissions for variant NM_001198800.3(ASCC1):c.871+1G>A

gnomAD frequency: 0.00001  dbSNP: rs763845791

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001882747	SCV002289796	likely pathogenic	not provided	2024-12-20	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 8 of the ASCC1 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 ASCC1 are known to be pathogenic (PMID: 30327447). This variant is present in population databases (rs763845791, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with clinical features of ASCC1-related conditions (PMID: 28749478, 37644014). ClinVar contains an entry for this variant (Variation ID: 1252053). 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.
GeneDx	RCV001882747	SCV005401449	pathogenic	not provided	2024-05-15	criteria provided, single submitter	clinical testing	Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32552793, 28749478)
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV001844369	SCV001870438	pathogenic	Spinal muscular atrophy with congenital bone fractures 2	2021-04-29	no assertion criteria provided	research