ClinVar Miner

Submissions for variant NM_032620.4(GTPBP3):c.592-1G>C

gnomAD frequency: 0.00004  dbSNP: rs763165541
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital RCV001733752 SCV001984623 likely pathogenic Combined oxidative phosphorylation defect type 23 2020-04-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001861043 SCV002267355 likely pathogenic not provided 2023-05-31 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 1301803). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with GTPBP3-related conditions. This variant is present in population databases (rs763165541, gnomAD 0.04%). This sequence change affects an acceptor splice site in intron 4 of the GTPBP3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in GTPBP3 are known to be pathogenic (PMID: 25434004).
Ambry Genetics RCV003346661 SCV004065874 uncertain significance Inborn genetic diseases 2023-07-17 criteria provided, single submitter clinical testing Resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNA decay Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Neuberg Centre For Genomic Medicine, NCGM RCV001733752 SCV004175752 likely pathogenic Combined oxidative phosphorylation defect type 23 criteria provided, single submitter clinical testing The observed invariant splice acceptor c.592-1G>C variant in GTPBP3 gene has been submitted to the ClinVar database as Likely Pathogenic. The c.592-1G>C variant has been reported with allele frequency of 0.004% in gnomAD Exomes. SpliceAI predicts this variant to cause splice acceptor loss (0.93) and splice acceptor gain (0.29). Loss of function variants in GTPBP3 gene have been previously reported to be disease causing (Kopajtich R, et al., 2014). However, additional functional studies will be required to prove the pathogenicity of this variant conclusively. For these reasons, this variant has been classified as Likely Pathogenic. In absence of another reportable variant in GTPBP3 gene, the molecular diagnosis is not confirmed.

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