Submissions for variant NR_023317.1(RNU7-1):n.28C>G

dbSNP: rs180837208

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001795577	SCV002034789	likely pathogenic	Aicardi-Goutieres syndrome 9	2021-07-28	criteria provided, single submitter	clinical testing	The RNU7-1 n.28C>G variant is a non-protein coding variant that has not been reported in the peer-reviewed literature. However, a different nucleotide change at the same position, n.28C>T, has been reported in at least six individuals with Aicardi-Goutieres syndrome and elevated levels of interferon (Uggenti et al. 2020); in two of these individuals, the n.28C>T variant was confirmed in trans with the n.40_47del variant. The n.28C>G variant is reported at a frequency of 0.000196 in the Latino/Admixed American population of the Genome Aggregation Database (version 3.1.1), a frequency that is consistent with a rare autosomal recessive disorder. Nucleotide 28 is a key position of the sm-binding site, and functional studies have shown that the n.28C>G nucleotide substitution inhibits the assembly and processing efficiency of the U7 snRNP (Kolev and Steiz 2006). Based on the evidence, the n.28C>G variant is classified as likely pathogenic for Aicardi-Goutieres syndrome.
CeGaT Center for Human Genetics Tuebingen	RCV004598147	SCV005092545	likely pathogenic	not provided	2024-07-01	criteria provided, single submitter	clinical testing	RNU7-1: PM3:Strong, PM2, PS1:Supporting
GeneDx	RCV004598147	SCV005333357	likely pathogenic	not provided	2024-01-29	criteria provided, single submitter	clinical testing	Observed with a second RNU7-1 variant in a patient with nystagmus, microcephaly, and dystonia, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (PMID: 37171742); Published functional studies demonstrate severely impaired RNU7-1 function (PMID: 16547514); Also known as n.28C>G; This variant is associated with the following publications: (PMID: 16547514, 33230297, 37171742)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001795577	SCV005887048	likely pathogenic	Aicardi-Goutieres syndrome 9	2025-01-27	criteria provided, single submitter	clinical testing	Variant summary: RNU7-1 n.28C>G alters a nucleotide in the non-coding RNA. The variant allele was found at a frequency of 6.9e-05 in 888472 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in RNU7-1 causing Aicardi-Goutieres syndrome 9 (6.9e-05 vs 0.0011), allowing no conclusion about variant significance. n.28C>G has been reported in the literature in at least one individual affected with Aicardi-Goutieres syndrome (example: Louise Frmond_2023). In functional studies the variant demonstrated impaired RNU7-1 function (Kolev_2006). The following publications have been ascertained in the context of this evaluation (PMID: 16547514, 37171742). ClinVar contains an entry for this variant (Variation ID: 1328141). Based on the evidence outlined above, the variant was classified as likely pathogenic.