Submissions for variant NM_000235.4(LIPA):c.538+4T>A

dbSNP: rs779872404

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001051986	SCV001216171	uncertain significance	Wolman disease	2021-08-27	criteria provided, single submitter	clinical testing	This sequence change falls in intron 5 of the LIPA gene. It does not directly change the encoded amino acid sequence of the LIPA protein. It affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with LIPA-related conditions. 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 is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005056837	SCV005726850	uncertain significance	not specified	2024-11-10	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001832477	SCV002091421	uncertain significance	Lysosomal acid lipase deficiency	2021-07-27	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004545030	SCV004783486	likely benign	LIPA-related disorder	2020-04-03	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).