ClinVar Miner

Submissions for variant NM_000191.3(HMGCL):c.348G>A (p.Ala116=)

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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 RCV002791758 SCV003196574 uncertain significance Deficiency of hydroxymethylglutaryl-CoA lyase 2022-07-15 criteria provided, single submitter clinical testing This sequence change affects codon 116 of the HMGCL mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the HMGCL protein. This variant also falls at the last nucleotide of exon 4, which is part of the consensus splice site for this exon. This variant is present in population databases (rs189198317, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with HMGCL-related conditions. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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.

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