Submissions for variant NM_000382.3(ALDH3A2):c.681-14T>G

dbSNP: rs1400349287

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000521423	SCV000617641	likely pathogenic	not provided	2017-08-31	criteria provided, single submitter	clinical testing	The c.681-14 T>G splice site variant has been previously reported in association with Sjögren-Larsson syndrome (Burgueño-Montañés et al., 2014). The variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant occurs at a nucleotide that is not conserved; however, several in-silico splice prediction models predict that c.681-14 T>G reduces the strength of the splice acceptor site of intron 4. Additionally, another variant at the same nucleotide has been reported in the Human Gene Mutation Database in association with Sjoegren-Larsson syndrome (Stenson et al., 2014). In the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. In summary, we consider this variant to be likely pathogenic.
Invitae	RCV000521423	SCV003441681	uncertain significance	not provided	2022-04-12	criteria provided, single submitter	clinical testing	This sequence change falls in intron 4 of the ALDH3A2 gene. It does not directly change the encoded amino acid sequence of the ALDH3A2 protein. This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has been observed in individual(s) with Sjögren–Larsson syndrome (PMID: 24377952). ClinVar contains an entry for this variant (Variation ID: 449458). 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 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.