Submissions for variant NM_007315.4(STAT1):c.1632+6G>A

gnomAD frequency: 0.00014  dbSNP: rs185216067

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000270500	SCV000425808	benign	Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000695283	SCV000823772	uncertain significance	Immunodeficiency 31B; Autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome; Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency	2023-10-18	criteria provided, single submitter	clinical testing	This sequence change falls in intron 19 of the STAT1 gene. It does not directly change the encoded amino acid sequence of the STAT1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs185216067, gnomAD 0.05%). This variant has been observed in individual(s) with autoimmune encephalitis (PMID: 35960392). ClinVar contains an entry for this variant (Variation ID: 333271). 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. 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.
CeGaT Center for Human Genetics Tuebingen	RCV003437061	SCV004148305	likely benign	not provided	2023-10-01	criteria provided, single submitter	clinical testing	STAT1: BP4