Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000489397 | SCV000577625 | likely pathogenic | not provided | 2015-12-28 | criteria provided, single submitter | clinical testing | The c.1102-3 C>G splice site variant in the TRMU gene has been previously reported in an individual with reversible infantile respiratory chain deficiency and hepatic failure who was also heterozygous for another variant in the TRMU gene (Uusimaa et al., 2011). This variant reduces the quality of the splice acceptor site in intron 10 and results in the creation of a new splice acceptor site 2 base pairs upstream of the canonical splice acceptor site, and is expected to cause abnormal gene splicing (Uusimaa et al., 2011). |
Invitae | RCV000489397 | SCV001577363 | likely pathogenic | not provided | 2023-12-19 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 10 of the TRMU gene. It does not directly change the encoded amino acid sequence of the TRMU protein. RNA analysis indicates that this variant induces altered splicing and likely disrupts the C-terminus of the protein. This variant is present in population databases (rs753039116, gnomAD 0.002%). This variant has been observed in individual(s) with acute infantile liver failure (PMID: 21931168). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 427012). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in activation of a cryptic splice site and introduces a new termination codon (PMID: 21931168). However the mRNA is not expected to undergo nonsense-mediated decay. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Baylor Genetics | RCV003476176 | SCV004204367 | likely pathogenic | Aminoglycoside-induced deafness | 2023-08-11 | criteria provided, single submitter | clinical testing | |
OMIM | RCV001274268 | SCV000045096 | pathogenic | Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins | 2011-10-01 | no assertion criteria provided | literature only | |
Natera, |
RCV001274268 | SCV001458234 | likely pathogenic | Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins | 2020-09-16 | no assertion criteria provided | clinical testing |