ClinVar Miner

Submissions for variant NR_003051.3(RMRP):n.147G>A (rs753874439)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000423744 SCV000515868 pathogenic not provided 2015-03-26 criteria provided, single submitter clinical testing The r.147 G>A variant has been reported previously as r.146 G>A in association with cartilage-hair hypoplasia (CHH), a disease with variable expressivity, which can present with defective cellular immunity presenting as a SCID phenotype (Thiel et al., 2007; Ridanpää et al., 2002). In vitro functional studiesdemonstrated that the c.147 G>A variant had the least effect on rRNA cleavage activity, which may explain why it is associated with a milder phenotype (Thiel et al., 2007). We interpret this variant as pathogenic.
Invitae RCV000549969 SCV000640108 likely pathogenic Anauxetic dysplasia 2018-12-17 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 present in population databases (rs753874439), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported as homozygous and in combination with other RMRP variants in individuals affected with RMRP-related diseases (PMID: 17701897, 12107819, Invitae). This variant is also known as r.146G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 379208). Experimental studies have shown that this variant elicits a mild functional impact as measured by immunodeficiency, hematological abnormalities, and CCNB2 mRNA cleavage activity (PMID: 17701897). A different variant affecting this nucleotide (n.147G>C) has also been reported in individuals affected with Cartilage Hair Hypoplasia (PMID: 16244706, Invitae). This suggests that this nucleotide is important for normal function of the gene and that other variants at this position may also be pathogenic. 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.
Counsyl RCV000666251 SCV000790510 likely pathogenic Metaphyseal chondrodysplasia, McKusick type 2017-03-31 no assertion criteria provided clinical testing

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