Submissions for variant NM_000035.4(ALDOB):c.113-1G>A

dbSNP: rs748663340

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001216380	SCV001388176	likely pathogenic	Hereditary fructosuria	2022-03-22	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 945681). Disruption of this splice site has been observed in individual(s) with hereditary fructose intolerance (PMID: 15880727). This variant is present in population databases (rs748663340, gnomAD 0.0009%). This sequence change affects an acceptor splice site in intron 2 of the ALDOB gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ALDOB are known to be pathogenic (PMID: 18541450).
ATS em Genética Clínica, Universidade Federal do Rio Grande do Sul	RCV001216380	SCV001573883	likely pathogenic	Hereditary fructosuria	2021-03-18	no assertion criteria provided	literature only