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NM_001243133.2(NLRP3):c.1297A>T (p.Thr433Ser) AND Cryopyrin associated periodic syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 7, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003760810.2

Allele description [Variation Report for NM_001243133.2(NLRP3):c.1297A>T (p.Thr433Ser)]

NM_001243133.2(NLRP3):c.1297A>T (p.Thr433Ser)

Gene:
NLRP3:NLR family pyrin domain containing 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q44
Genomic location:
Preferred name:
NM_001243133.2(NLRP3):c.1297A>T (p.Thr433Ser)
HGVS:
  • NC_000001.11:g.247424746A>T
  • NG_007509.2:g.13574A>T
  • NM_001079821.3:c.1297A>T
  • NM_001127461.3:c.1297A>T
  • NM_001127462.3:c.1297A>T
  • NM_001243133.2:c.1297A>TMANE SELECT
  • NM_004895.5:c.1303A>T
  • NM_183395.3:c.1297A>T
  • NP_001073289.2:p.Thr433Ser
  • NP_001120933.2:p.Thr433Ser
  • NP_001120934.2:p.Thr433Ser
  • NP_001230062.1:p.Thr433Ser
  • NP_004886.3:p.Thr435Ser
  • NP_004886.3:p.Thr435Ser
  • NP_899632.2:p.Thr433Ser
  • LRG_197t1:c.1303A>T
  • LRG_197:g.13574A>T
  • LRG_197p1:p.Thr435Ser
  • NC_000001.10:g.247588048A>T
  • NM_004895.4:c.1303A>T
Protein change:
T433S
Molecular consequence:
  • NM_001079821.3:c.1297A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127461.3:c.1297A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127462.3:c.1297A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243133.2:c.1297A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004895.5:c.1303A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_183395.3:c.1297A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cryopyrin associated periodic syndrome (CAPS)
Identifiers:
MONDO: MONDO:0016168; MedGen: C2316212

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004413667Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 7, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

High incidence of NLRP3 somatic mosaicism in patients with chronic infantile neurologic, cutaneous, articular syndrome: results of an International Multicenter Collaborative Study.

Tanaka N, Izawa K, Saito MK, Sakuma M, Oshima K, Ohara O, Nishikomori R, Morimoto T, Kambe N, Goldbach-Mansky R, Aksentijevich I, de Saint Basile G, Neven B, van Gijn M, Frenkel J, Aróstegui JI, Yagüe J, Merino R, Ibañez M, Pontillo A, Takada H, Imagawa T, et al.

Arthritis Rheum. 2011 Nov;63(11):3625-32. doi: 10.1002/art.30512.

PubMed [citation]
PMID:
21702021
PMCID:
PMC3498501

Hereditary autoinflammatory syndromes: a Brazilian multicenter study.

Jesus AA, Fujihira E, Watase M, Terreri MT, Hilario MO, Carneiro-Sampaio M, Len CA, Oliveira SK, Rodrigues MC, Pereira RM, Bica B, Silva NA, Cavalcanti A, Marini R, Sztajnbok F, Quintero MV, Ferriani VP, Moraes-Vasconcelos D, Silva CA, Oliveira JB.

J Clin Immunol. 2012 Oct;32(5):922-32. doi: 10.1007/s10875-012-9688-x. Epub 2012 May 8. Erratum in: J Clin Immunol. 2012 Oct;32(5):933-5.

PubMed [citation]
PMID:
22566169
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004413667.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 435 of the NLRP3 protein (p.Thr435Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with NLRP3-related conditions (PMID: 21702021, 22566169, 26316056). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NLRP3 protein function. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024