ClinVar Miner

Submissions for variant NM_014444.5(TUBGCP4):c.579dup (p.Gly194fs)

gnomAD frequency: 0.00004  dbSNP: rs794726855
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000170358 SCV000597743 pathogenic Microcephaly and chorioretinopathy 3 2016-07-26 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001212073 SCV001383646 pathogenic not provided 2024-11-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly194Trpfs*8) in the TUBGCP4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TUBGCP4 are known to be pathogenic (PMID: 25817018). This variant is present in population databases (rs765297510, gnomAD 0.2%). This premature translational stop signal has been observed in individual(s) with clinical features of microcephaly and chorioretinal dysplasia (PMID: 25817018). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 190124). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001212073 SCV001793028 pathogenic not provided 2023-08-24 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 34313030, 25817018)
Revvity Omics, Revvity RCV000170358 SCV004238786 likely pathogenic Microcephaly and chorioretinopathy 3 2023-07-12 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000170358 SCV005394593 pathogenic Microcephaly and chorioretinopathy 3 2024-09-25 criteria provided, single submitter clinical testing Variant summary: TUBGCP4 c.579dupT (p.Gly194TrpfsX8) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 0.00012 in 249472 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in TUBGCP4 causing Microcephaly And Chorioretinopathy 3, allowing no conclusion about variant significance. c.579dupT has been reported in the literature in two compound heterozygous individuals in a family affected with Microcephaly And Chorioretinopathy 3 (Scheidecker_2015). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 25817018). ClinVar contains an entry for this variant (Variation ID: 190124). Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000170358 SCV000222767 pathogenic Microcephaly and chorioretinopathy 3 2015-04-02 no assertion criteria provided literature only

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