Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002731142 | SCV003009621 | pathogenic | not provided | 2022-05-17 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with POLR3A-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change creates a premature translational stop signal (p.Arg229*) in the POLR3A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POLR3A are known to be pathogenic (PMID: 21855841, 25339210, 27612211, 30414627, 30450527). |
| Ambry Genetics | RCV003274013 | SCV003963142 | pathogenic | Inborn genetic diseases | 2023-03-29 | criteria provided, single submitter | clinical testing | The c.685C>T (p.R229*) alteration, located in exon 6 (coding exon 6) of the POLR3A gene, consists of a C to T substitution at nucleotide position 685. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 229. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the T allele has an overall frequency of 0.001% (3/251296) total alleles studied. The highest observed frequency was 0.005% (1/21590) of European (Finnish) alleles. This variant has been reported to be compound heterozygous with the recurrent hypomorphic c.1909+22G>A allele in an individual with features consistent with POLR3A-related ataxia (Baviera-Muñoz, 2022). Based on the available evidence, this alteration is classified as pathogenic. |