Submissions for variant NM_022464.5(SIL1):c.1029+1G>A

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000002744	SCV005812501	pathogenic	Marinesco-Sjögren syndrome	2024-03-12	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 9 of the SIL1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. Disruption of this splice site has been observed in individual(s) with Marinesco-Sjogren syndrome (PMID: 16282977). ClinVar contains an entry for this variant (Variation ID: 2626). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the SIL1 protein in which other variant(s) (p.Gln414*) have been determined to be pathogenic (PMID: 19471582). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
OMIM	RCV000002744	SCV000022902	pathogenic	Marinesco-Sjögren syndrome	2005-12-01	no assertion criteria provided	literature only