ClinVar Miner

Submissions for variant NM_001243133.2(NLRP3):c.224C>T (p.Ala75Val)

dbSNP: rs200288250
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001200569 SCV000278932 likely benign not provided 2021-02-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 32707200)
Invitae RCV000690646 SCV000818343 likely benign Cryopyrin associated periodic syndrome 2024-01-29 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000213778 SCV001365745 uncertain significance not specified 2019-06-28 criteria provided, single submitter clinical testing The p.Ala77Val variant in NLRP3 has not been previously reported in individuals with hearing loss or Cryopyrin-associated periodic syndromes, but has been identified in 0.01% (6/30606) of South Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant has also been reported in ClinVar (Variation ID 234286). Computational prediction tools and conservation analysis suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: BP4.
CeGaT Center for Human Genetics Tuebingen RCV001200569 SCV001371566 uncertain significance not provided 2020-04-01 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002262812 SCV002542618 uncertain significance Autoinflammatory syndrome 2021-04-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV002519742 SCV003715615 uncertain significance Inborn genetic diseases 2020-11-20 criteria provided, single submitter clinical testing The c.230C>T (p.A77V) alteration is located in exon 1 (coding exon 1) of the NLRP3 gene. This alteration results from a C to T substitution at nucleotide position 230, causing the alanine (A) at amino acid position 77 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004532810 SCV004118390 uncertain significance NLRP3-related disorder 2023-01-05 criteria provided, single submitter clinical testing The NLRP3 c.230C>T variant is predicted to result in the amino acid substitution p.Ala77Val. This variant was reported in an individual with presumed ocular histoplasmosis syndrome (POHS, Li et al. 2020. PubMed ID: 32707200). This variant is reported in 0.020% of alleles in individuals of South Asian descent in gnomAD, which may be too common to be causative of autosomal dominant disorders (http://gnomad.broadinstitute.org/variant/1-247582326-C-T). While we suspect 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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