ClinVar Miner

Submissions for variant NR_023343.3(RNU4ATAC):n.124G>A

gnomAD frequency: 0.00004  dbSNP: rs544312701
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Undiagnosed Diseases Network, NIH RCV002251939 SCV002523167 likely pathogenic Roifman syndrome 2022-01-27 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002514136 SCV003524947 pathogenic not provided 2023-12-01 criteria provided, single submitter clinical testing This variant occurs in the RNU4ATAC gene, which encodes an RNA molecule that does not result in a protein product. This variant is present in population databases (rs544312701, gnomAD 0.02%). This variant has been observed in individual(s) with microcephalic osteodysplastic primordial dwarfism, type I (PMID: 22581640, 27040866). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 39443). Functional studies have shown that this variant disrupts ncRNA function (PMID: 24865609) This variant is located within the Sm protein-binding region of the RNU4ATAC RNA, which is important for small nuclear RNA maturation (PMID: 32628740). A significant number of disease-associated RNU4ATAC variants are found in this region (PMID: 32628740, 30368667). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002251939 SCV004029993 likely pathogenic Roifman syndrome 2023-07-19 criteria provided, single submitter clinical testing Variant summary: RNU4ATAC n.124G>A alters a nucleotide in the non-coding RNA. The variant allele was found at a frequency of 6.1e-05 in 130472 control chromosomes. n.124G>A has been reported in the literature in individuals affected with Microcephalic Osteodysplastic Primordial Dwarfism type I (Putoux_2016, Abdel-Salaam_2012). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence demonstrating a greater than 90% decrease in snRNA (Jafarifar_2014). The following publications have been ascertained in the context of this evaluation (PMID: 22581640, 24865609, 27040866). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic (n=1) and likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as likely pathogenic.
OMIM RCV000032638 SCV000056401 pathogenic Osteodysplastic primordial dwarfism, type 1 2012-06-01 no assertion criteria provided literature only

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