Submissions for variant NR_003051.4(RMRP):n.197C>T

dbSNP: rs948931144

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000814860	SCV000955292	pathogenic	Anauxetic dysplasia	2024-12-05	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 0.03%). This variant has been observed in individual(s) with cartilage-hair hypoplasia-anauxetic dysplasia spectrum disorders (PMID: 11940090, 12107819, 16244706, 16838329, 17701897). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as 195C>T. ClinVar contains an entry for this variant (Variation ID: 633393). Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects RMRP function (PMID: 11701897). For these reasons, this variant has been classified as Pathogenic.
AiLife Diagnostics, AiLife Diagnostics	RCV002223939	SCV002503487	pathogenic	not provided	2022-01-17	criteria provided, single submitter	clinical testing
Shenzhen Maternity and Child Healthcare Hospital, Institute of Maternal and Child Medicine Research	RCV000781815	SCV005328392	pathogenic	Metaphyseal chondrodysplasia, McKusick type		criteria provided, single submitter	clinical testing	The RMRP n.196C>T (also known as n.195C>T) variant involves the alteration of a conserved nucleotide in the RMRP gene, which encodes an RNA molecule that does not result in a protein product. This variant, along with other mutations, has been observed to form a compound heterozygous mutation in individual(s) with cartilage-hair hypoplasia-anauxetic dysplasia spectrum disorders (PMID: 11940090, 32021596, 17701897, 16838329, 16244706, 12107819). 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 (PMID: 17701897). For these reasons , this variant was classified as pathogenic.
OMIM	RCV000015285	SCV000035544	pathogenic	Metaphyseal dysplasia without hypotrichosis	2002-02-01	no assertion criteria provided	literature only
Natera, Inc.	RCV000781815	SCV002077503	pathogenic	Metaphyseal chondrodysplasia, McKusick type	2020-12-31	no assertion criteria provided	clinical testing