Submissions for variant NM_144687.4(NLRP12):c.2960G>A (p.Cys987Tyr)

gnomAD frequency: 0.00010  dbSNP: rs369502542

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000807340	SCV000947388	uncertain significance	Familial cold autoinflammatory syndrome 2	2024-09-29	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 987 of the NLRP12 protein (p.Cys987Tyr). This variant is present in population databases (rs369502542, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with NLRP12-related conditions. ClinVar contains an entry for this variant (Variation ID: 651898). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Illumina Laboratory Services, Illumina	RCV000807340	SCV001290571	benign	Familial cold autoinflammatory syndrome 2	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.
Ambry Genetics	RCV004649333	SCV005144987	uncertain significance	Inborn genetic diseases	2024-05-29	criteria provided, single submitter	clinical testing	The c.2960G>A (p.C987Y) alteration is located in exon 9 (coding exon 9) of the NLRP12 gene. This alteration results from a G to A substitution at nucleotide position 2960, causing the cysteine (C) at amino acid position 987 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.