ClinVar Miner

Submissions for variant NM_000516.7(GNAS):c.312+5G>C

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003560147 SCV004298105 likely pathogenic not provided 2023-12-09 criteria provided, single submitter clinical testing This sequence change falls in intron 4 of the GNAS gene. It does not directly change the encoded amino acid sequence of the GNAS protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with pseudohypoparathyroidism (PMID: 27922245; Invitae). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the c.312+5G nucleotide in the GNAS gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 18089698, 29059381). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. 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.

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