Submissions for variant NM_144687.4(NLRP12):c.779C>T (p.Thr260Met)

gnomAD frequency: 0.00027  dbSNP: rs150280940

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001080546	SCV000414556	benign	Familial cold autoinflammatory syndrome 2	2018-01-12	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.
GeneDx	RCV000481155	SCV000571347	uncertain significance	not provided	2018-03-27	criteria provided, single submitter	clinical testing	The T260M variant in the NLRP12 gene has not been reported previously as a pathogenic, nor as a benign variant in a peer reviewed journal article to our knowledge. The T260M variant is observed in 40/16508 (0.25%) alleles from individuals of South Asian background in the ExAC dataset (Lek et al., 2016). This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret T260M as a variant of uncertain significance.
Invitae	RCV001080546	SCV000767409	likely benign	Familial cold autoinflammatory syndrome 2	2024-01-18	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002263584	SCV002542567	uncertain significance	Autoinflammatory syndrome	2022-04-25	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000481155	SCV004033701	likely benign	not provided	2023-08-01	criteria provided, single submitter	clinical testing	NLRP12: BP4, BS1
Mayo Clinic Laboratories, Mayo Clinic	RCV000481155	SCV004225438	uncertain significance	not provided	2022-07-13	criteria provided, single submitter	clinical testing	BS2, PM6_supporting
PreventionGenetics, part of Exact Sciences	RCV003922406	SCV004739331	likely benign	NLRP12-related disorder	2021-07-29	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).