ClinVar Miner

Submissions for variant NM_000190.4(HMBS):c.874C>T (p.Gln292Ter)

dbSNP: rs1592220915
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000807669 SCV000947735 pathogenic not provided 2021-10-10 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the HMBS protein. Other variant(s) that disrupt this region (p.Gln328Valfs*30, p.Leu329Phefs*30, p.Gly335Alafs*9, and p.Arg355Profs*4) have been observed in individuals with HMBS-related conditions (PMID: 8168829, 9463797, 9702975, 10944860, 19138865). This suggests that this may be a clinically significant region of the protein. ClinVar contains an entry for this variant (Variation ID: 652166). This premature translational stop signal has been observed in individuals with acute intermittent porphyria (PMID: 10782018, 11831862). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln292*) in the HMBS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 70 amino acid(s) of the HMBS protein.
3billion RCV003152735 SCV003841666 likely pathogenic Acute intermittent porphyria 2023-02-23 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. This variant was predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by more than 10%. The variant has been reported to be associated with HMBS related disorder (ClinVar ID: VCV000652166 / PMID: 10782018). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV003152735 SCV004807840 likely pathogenic Acute intermittent porphyria 2024-03-29 criteria provided, single submitter clinical testing

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