Submissions for variant NR_003051.4(RMRP):n.52C>T

dbSNP: rs1064793373

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000487375	SCV000565950	likely pathogenic	not provided	2015-03-20	criteria provided, single submitter	clinical testing	To our knowledge, the r.(51 c>u) variant has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism. The r.(51 c>u) variant is located in the stem region close to the P3 domain of RMRP. This substitution occurs at a position that is well conserved across species, with T" only being observed in the megabat species. The r.(51 c>u) variant changes a Watson-Crick base pair to a T:G wobble base pair. In addition, a known variant r.(41 g>a) at an adjacent Watson-Crick base pair in the same stem region and other regulatory mutations have been reported in the Human Gene Mutation Database in association with Cartilage-Hair hypoplasia (Stenson et al., 2014). Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded."
Counsyl	RCV000669352	SCV000794098	uncertain significance	Metaphyseal chondrodysplasia, McKusick type	2017-09-11	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001844172	SCV002104163	uncertain significance	not specified	2022-02-16	criteria provided, single submitter	clinical testing	Variant summary: RMRP n.51C>T alters a nucleotide in the non-coding RNA. The variant allele was found at a frequency of 2.3e-05 in 130464 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of n.51C>T in individuals affected with Cartilage-Hair Hypoplasia and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance and likely pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance until additional clinical and functional evidence become available.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001851143	SCV002178356	uncertain significance	Anauxetic dysplasia	2023-12-25	criteria provided, single submitter	clinical testing	This variant occurs in the RMRP gene, which encodes an RNA molecule that does not result in a protein product. This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has been observed in individual(s) with T cell lymphopenia (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 418696). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen	RCV000487375	SCV002564047	uncertain significance	not provided	2019-11-01	criteria provided, single submitter	clinical testing