Submissions for variant NM_001080.3(ALDH5A1):c.1474G>A (p.Val492Ile)

gnomAD frequency: 0.00032  dbSNP: rs151294087

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000426165	SCV000510607	uncertain significance	not provided	2016-04-25	criteria provided, single submitter	clinical testing	Converted during submission to Uncertain significance.
GeneDx	RCV000426165	SCV000564553	uncertain significance	not provided	2023-07-02	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae	RCV000634927	SCV000756299	likely benign	Succinate-semialdehyde dehydrogenase deficiency	2024-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002282135	SCV002572124	uncertain significance	not specified	2022-08-18	criteria provided, single submitter	clinical testing	Variant summary: ALDH5A1 c.1474G>A (p.Val492Ile) results in a conservative amino acid change located in the aldehyde dehydrogenase domain (IPR015590) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00017 in 251490 control chromosomes, predominantly at a frequency of 0.0011 within the African or African-American subpopulation in the gnomAD database. To our knowledge, no occurrence of c.1474G>A in individuals affected with Succinic Semialdehyde Dehydrogenase Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have provided clinical-significance assessments for this variant to ClinVar after 2014. Two classified the variant as VUS and the other classified it as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics	RCV002524702	SCV003650064	uncertain significance	Inborn genetic diseases	2021-07-06	criteria provided, single submitter	clinical testing	The c.1474G>A (p.V492I) alteration is located in exon 10 (coding exon 10) of the ALDH5A1 gene. This alteration results from a G to A substitution at nucleotide position 1474, causing the valine (V) at amino acid position 492 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GenomeConnect, ClinGen	RCV000634927	SCV000840263	not provided	Succinate-semialdehyde dehydrogenase deficiency		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.