ClinVar Miner

Submissions for variant NM_144687.4(NLRP12):c.3128C>T (p.Thr1043Ile)

gnomAD frequency: 0.00011  dbSNP: rs143874173
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000821660 SCV000962429 uncertain significance Familial cold autoinflammatory syndrome 2 2024-06-11 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1043 of the NLRP12 protein (p.Thr1043Ile). This variant is present in population databases (rs143874173, gnomAD 0.02%). 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: 663725). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Ambry Genetics RCV002537509 SCV003568548 uncertain significance Inborn genetic diseases 2022-09-22 criteria provided, single submitter clinical testing The c.3128C>T (p.T1043I) alteration is located in exon 10 (coding exon 10) of the NLRP12 gene. This alteration results from a C to T substitution at nucleotide position 3128, causing the threonine (T) at amino acid position 1043 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003396447 SCV004111827 uncertain significance NLRP12-related disorder 2023-03-20 criteria provided, single submitter clinical testing The NLRP12 c.3128C>T variant is predicted to result in the amino acid substitution p.Thr1043Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.024% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-54297361-G-A), which may be too common to be causative of disease. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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