ClinVar Miner

Submissions for variant NR_003051.3(RMRP):n.-25_-3dup (rs1554651413)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666857 SCV000791219 likely pathogenic Metaphyseal chondrodysplasia, McKusick type 2017-05-04 criteria provided, single submitter clinical testing
Invitae RCV000809273 SCV000949419 likely pathogenic Anauxetic dysplasia 2018-09-01 criteria provided, single submitter clinical testing This sequence change occurs in the RMRP gene, which encodes the RNA component of the RNase mitochondrial RNA processing (MRP) complex and does not result in a protein product. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. While this particular variant has not been reported in the literature, it is located in the promoter region between the TATA box and the transcription initiation site, and other similar insertions and duplications immediately upstream of the coding sequence have been reported in individuals affected with cartilage-hair hypoplasia (PMID: 11207361, 16838329, 17189938, 21570718). While functional studies for this variant have not been reported, experimental analyses using patient derived cells, as well as in vitro transfection studies, have shown that promoter insertions result in silencing of RMRP transcription and reduced expression of the gene product (PMID: 11207361, 16254002). 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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