ClinVar Miner

Submissions for variant NM_003239.5(TGFB3):c.927-1G>C

dbSNP: rs767548724
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000576406 SCV000678235 likely pathogenic Rienhoff syndrome 2017-08-01 criteria provided, single submitter clinical testing TGFB3 NM_003239 exon 6 c.927-1G>C: This variant has not been previously reported in the literature but has been identified in 1/33572 Latino chromosomes in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs767548724). This variant alters the consensus splice sequence (+/- 1,2) which is predicted to result in an absent or abnormal protein. Loss of function has been reported as a disease mechanism for this gene and disease (Bertoli-Avella, 2015 PMID:25835445). In summary, data on this variant is highly suspicious for disease, but requires further evidence for pathogenicity. Therefore, this variant classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000576406 SCV001225146 likely pathogenic Rienhoff syndrome 2022-10-16 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 5 of the TGFB3 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 TGFB3 are known to be pathogenic (PMID: 25835445, 26188975). This variant is present in population databases (rs767548724, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with TGFB3-related conditions. ClinVar contains an entry for this variant (Variation ID: 487471). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV002060544 SCV002495984 likely pathogenic Arrhythmogenic right ventricular dysplasia 1; Rienhoff syndrome 2021-12-22 criteria provided, single submitter clinical testing TGFB3 NM_003239 exon 6 c.927-1G>C: This variant has not been previously reported in the literature but has been identified in 1/33572 Latino chromosomes in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs767548724). This variant alters the consensus splice sequence (+/- 1,2) which is predicted to result in an absent or abnormal protein. Loss of function has been reported as a disease mechanism for this gene and disease (Bertoli-Avella, 2015 PMID:25835445). In summary, data on this variant is highly suspicious for disease, but requires further evidence for pathogenicity. Therefore, this variant classified as likely pathogenic.

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