ClinVar Miner

Submissions for variant NM_007055.4(POLR3A):c.3388G>A (p.Val1130Ile)

gnomAD frequency: 0.00006  dbSNP: rs199581222
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001350255 SCV001544643 uncertain significance not provided 2022-10-24 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1130 of the POLR3A protein (p.Val1130Ile). This variant is present in population databases (rs199581222, gnomAD 0.09%). This variant has not been reported in the literature in individuals affected with POLR3A-related conditions. ClinVar contains an entry for this variant (Variation ID: 816787). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt POLR3A protein function. 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.
Ambry Genetics RCV002549268 SCV003756351 uncertain significance Inborn genetic diseases 2022-07-27 criteria provided, single submitter clinical testing The c.3388G>A (p.V1130I) alteration is located in exon 26 (coding exon 26) of the POLR3A gene. This alteration results from a G to A substitution at nucleotide position 3388, causing the valine (V) at amino acid position 1130 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV001350255 SCV004012470 uncertain significance not provided 2023-06-07 criteria provided, single submitter clinical testing Reported previously in the homozygous state in a patient with multiple joint contractures, delayed motor milestones, dysmorphic features, and cerebellar vermis hypoplasia who also had a homozygous variant in another gene thought to be likely related to the arthrogryposis; parents were found to be carriers but no clinical information was provided (Bayram et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26752647, 36385762)
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV001007775 SCV001167459 uncertain significance Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome no assertion criteria provided research

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.