Submissions for variant NM_000191.3(HMGCL):c.497+4A>G

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Minimum conflict level: Report conflict between different conditions
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Total submissions: 3

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000498294	SCV000589487	likely pathogenic	not provided	2015-10-05	criteria provided, single submitter	clinical testing	An individual with symptoms associated with HMG-CoA lyase deficiency was heterozygous for this variant and a nonsense variant; however, parental testing was not done to confirm the variants were in trans (Menao et al., 2009). Functional analysis found that the c.497+4 A>G variant results in alternative splicing with 2 transcripts, one bearing a five-exon deletion and the other with deletion of exons 5 and 6 (Menao et al., 2009). Additionally, this nucleotide substitution occurs at a position that is conserved across species and several in-silico splice prediction models predict that c.497+4 A>G creates a cryptic donor site in intron 5. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Counsyl	RCV000665452	SCV000789581	uncertain significance	Deficiency of hydroxymethylglutaryl-CoA lyase	2017-02-14	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000665452	SCV004199880	likely pathogenic	Deficiency of hydroxymethylglutaryl-CoA lyase	2024-01-20	criteria provided, single submitter	clinical testing

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