Submissions for variant NM_144687.4(NLRP12):c.2757-1G>T

gnomAD frequency: 0.00001  dbSNP: rs143515989

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001913172	SCV002175980	uncertain significance	Familial cold autoinflammatory syndrome 2	2023-05-20	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with NLRP12-related conditions. This variant is present in population databases (rs143515989, gnomAD 0.003%). This sequence change affects an acceptor splice site in intron 7 of the NLRP12 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), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in NLRP12 cause disease. ClinVar contains an entry for this variant (Variation ID: 1401846). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002264423	SCV002542522	likely pathogenic	Autoinflammatory syndrome	2017-12-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003426242	SCV004142679	uncertain significance	not provided	2023-08-01	criteria provided, single submitter	clinical testing