ClinVar Miner

Submissions for variant NM_000191.3(HMGCL):c.252+1G>C

dbSNP: rs775218067
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003054546 SCV003337728 likely pathogenic Deficiency of hydroxymethylglutaryl-CoA lyase 2022-04-21 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 3 of the HMGCL gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (PMID: 11129331, 19036343). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that disruption of this splice site affects HMGCL function (PMID: 11129331). Studies have shown that disruption of this splice site results in skipping of exon 3, but is expected to preserve the integrity of the reading-frame (PMID: 19036343). 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.

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