NM_001243133.2(NLRP3):c.1316C>T (p.Ala439Val) AND Cryopyrin associated periodic syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 20, 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:: RCV000701554.16

Allele description [Variation Report for NM_001243133.2(NLRP3):c.1316C>T (p.Ala439Val)]

NM_001243133.2(NLRP3):c.1316C>T (p.Ala439Val)

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.1316C>T (p.Ala439Val)

HGVS:

NC_000001.11:g.247424765C>T
NG_007509.2:g.13593C>T
NM_001079821.3:c.1316C>T
NM_001127461.3:c.1316C>T
NM_001127462.3:c.1316C>T
NM_001243133.2:c.1316C>TMANE SELECT
NM_004895.5:c.1322C>T
NM_183395.3:c.1316C>T
NP_001073289.2:p.Ala439Val
NP_001120933.2:p.Ala439Val
NP_001120934.2:p.Ala439Val
NP_001230062.1:p.Ala439Val
NP_001230062.1:p.Ala439Val
NP_004886.3:p.Ala441Val
NP_004886.3:p.Ala441Val
NP_899632.2:p.Ala439Val
LRG_197t1:c.1322C>T
LRG_197:g.13593C>T
LRG_197p1:p.Ala441Val
NC_000001.10:g.247588067C>T
NM_001243133.1:c.1316C>T
NM_004895.4:c.1322C>T

Protein change:

A439V; ALA439VAL

Links:

OMIM: 606416.0001; dbSNP: rs121908146

NCBI 1000 Genomes Browser:

rs121908146

Molecular consequence:

NM_001079821.3:c.1316C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127461.3:c.1316C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127462.3:c.1316C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001243133.2:c.1316C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004895.5:c.1322C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_183395.3:c.1316C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000830359	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 20, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 11687797, 15801036, 25596455, 26245507, 26931528, 27134254, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000830359

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 20, 2023)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome.

Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD.

Nat Genet. 2001 Nov;29(3):301-5.

PubMed [citation]

PMID:: 11687797
PMCID:: PMC4322000

Intrafamilial variable phenotypic expression of a CIAS1 mutation: from Muckle-Wells to chronic infantile neurological cutaneous and articular syndrome.

Hentgen V, Despert V, Leprêtre AC, Cuisset L, Chevrant-Breton J, Jégo P, Chalès G, Gall EL, Delpech M, Grateau G.

J Rheumatol. 2005 Apr;32(4):747-51.

PubMed [citation]

PMID:: 15801036

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000830359.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 4370). This variant is also known as A439V or C1316T. This missense change has been observed in individuals with NLRP3-related disease (PMID: 11687797, 15801036, 25596455, 26245507, 26931528, 27134254). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 441 of the NLRP3 protein (p.Ala441Val).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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