ClinVar Miner

Submissions for variant NM_018006.5(TRMU):c.1102-3C>G

gnomAD frequency: 0.00002  dbSNP: rs753039116
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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, Inc. 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

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