Submissions for variant NM_005051.3(QARS1):c.117+5G>A

gnomAD frequency: 0.00042  dbSNP: rs151099269

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000655200	SCV000777125	uncertain significance	Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome	2022-10-24	criteria provided, single submitter	clinical testing	This sequence change falls in intron 1 of the QARS gene. It does not directly change the encoded amino acid sequence of the QARS protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs151099269, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with QARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 544146). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
GeneDx	RCV001577835	SCV001805302	uncertain significance	not provided	2024-06-18	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis indicates that this variant does not alter splicing
Revvity Omics, Revvity	RCV000655200	SCV003810435	uncertain significance	Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome	2022-01-20	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001577835	SCV003924232	uncertain significance	not provided	2021-03-30	criteria provided, single submitter	clinical testing	QARS NM_005051 exon 1 c.117+5G>A: This variant has not been reported in the literature but is present in 0.1% (43/23664) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs151099269). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is an intronic variant with no predicted change in the amino acid sequence but may have an unknown effect on splicing. Further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.