ClinVar Miner

Submissions for variant NM_000190.4(HMBS):c.445C>T (p.Arg149Ter)

dbSNP: rs118204120
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000001551 SCV000492655 pathogenic Acute intermittent porphyria 2015-11-25 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001389642 SCV001591075 pathogenic not provided 2023-09-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg149*) in the HMBS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HMBS are known to be pathogenic (PMID: 7757070, 7962538). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with acute intermittent porphyria (PMID: 7757070, 25118551, 27507172). ClinVar contains an entry for this variant (Variation ID: 1486). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000001551 SCV000021706 pathogenic Acute intermittent porphyria 2006-01-01 no assertion criteria provided literature only
PreventionGenetics, part of Exact Sciences RCV003924793 SCV004737463 pathogenic HMBS-related disorder 2023-11-21 no assertion criteria provided clinical testing The HMBS c.445C>T variant is predicted to result in premature protein termination (p.Arg149*). This variant was reported in individuals with acute intermittent porphyria phenotypes (Table 1, Kauppinen et al. 1995. PubMed ID: 7757070; Ribeiro et al. 2002. PubMed ID: 12357456). This variant has not been reported in a large population database, indicating this variant is rare. Nonsense variants in HMBS are expected to be pathogenic. This variant is interpreted as pathogenic.

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