Submissions for variant NM_139276.3(STAT3):c.1140-3C>T

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003787476	SCV004576519	uncertain significance	Hyper-IgE recurrent infection syndrome 1, autosomal dominant; STAT3 gain of function	2023-10-05	criteria provided, single submitter	clinical testing	This sequence change falls in intron 12 of the STAT3 gene. It does not directly change the encoded amino acid sequence of the STAT3 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs201833309, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with STAT3-related conditions. 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 is not likely to affect RNA splicing. This variant disrupts the c.1140-3C nucleotide in the STAT3 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 29803798). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.