ClinVar Miner

Submissions for variant NR_003051.3(RMRP):n.196C>T (rs948931144)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000781815 SCV000920153 pathogenic Metaphyseal chondrodysplasia, McKusick type 2018-05-04 criteria provided, single submitter clinical testing Variant summary: The RMRP n.196C>T (also known as n.195C>T) variant involves the alteration of a conserved nucleotide. The variant allele was found at a frequency of 8e-05 in 125446 control chromosomes (gnomAD and publications). This frequency is not higher than expected for a pathogenic variant in RMRP causing Cartilage-Hair Hypoplasia (8e-05 vs. 7.20e-03), allowing no conclusion about variant significance. The variant, n.196c>t, has been reported in the literature in multiple individuals affected with Cartilage-Hair Hypoplasia and Anauxetic Dysplasia (Thiel 2007, Bonafe 2005, Hermanns 2006, Ridanpaa 2002). These data indicate that the variant is very likely to be associated with disease. One publication reports experimental evidence showing a mild to intermediate decrease in RNA cleavage activities associated with this variant (Thiel 2007). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000814860 SCV000955292 likely pathogenic Anauxetic dysplasia 2018-08-14 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. This variant has been observed in numerous individuals affected with cartilage-hair hypoplasia-anauxetic dysplasia spectrum disorders (PMID: 16838329, 11940090, 16244706, 17701897, 12107819). This variant is also known as 195C>T in the literature. Experimental studies have shown that this sequence change results in mildly impaired cleavage activity (PMID: 11701897). 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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