ClinVar Miner

Submissions for variant NM_000191.3(HMGCL):c.144+1G>A

gnomAD frequency: 0.00001  dbSNP: rs1638698732
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001378372 SCV001575924 likely pathogenic Deficiency of hydroxymethylglutaryl-CoA lyase 2020-09-20 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 2 of the HMGCL gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with HMGCL-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in HMGCL are known to be pathogenic (PMID: 9817922, 17692550, 23465862). 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.
Natera, Inc. RCV001831353 SCV002094167 likely pathogenic Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency 2017-06-16 no assertion criteria provided clinical testing

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