Submissions for variant NM_001080.3(ALDH5A1):c.1343+1_1343+3delinsTT

dbSNP: rs875989801

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Revvity Omics, Revvity	RCV000211103	SCV002024295	pathogenic	Succinate-semialdehyde dehydrogenase deficiency	2020-11-20	criteria provided, single submitter	clinical testing
Elsea Laboratory, Baylor College of Medicine	RCV000211103	SCV002820035	pathogenic	Succinate-semialdehyde dehydrogenase deficiency	2021-03-08	criteria provided, single submitter	curation
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000211103	SCV000268064	pathogenic	Succinate-semialdehyde dehydrogenase deficiency	2016-04-28	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001355716	SCV001550673	likely pathogenic	not provided		no assertion criteria provided	clinical testing	The ALDH5A1 c.1382+1_1382+3delinsTT variant was not identified in the literature but was identified in dbSNP (ID: rs875989801) and ClinVar (classified as pathogenic by Genomic Research Center, Shahid Beheshti University of Medical Sciences). The variant was not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, or the Genome Aggregation Database (March 6, 2019, v2.1.1). The c.1382+1_1382+3delinsTT variant is predicted to cause abnormal splicing because the nucleotide substitution occurs in the invariant region of the splice consensus sequence. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a difference in splicing and the loss of the canonical 5' splice site. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more pathogenic role for this variant. This variant is classified as likely pathogenic.