NM_001243133.2(NLRP3):c.2012G>C (p.Cys671Ser) AND Cryopyrin associated periodic syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 27, 2020
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:: RCV000818510.7

Allele description [Variation Report for NM_001243133.2(NLRP3):c.2012G>C (p.Cys671Ser)]

NM_001243133.2(NLRP3):c.2012G>C (p.Cys671Ser)

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.2012G>C (p.Cys671Ser)

HGVS:

NC_000001.11:g.247425461G>C
NG_007509.2:g.14289G>C
NM_001079821.3:c.2012G>C
NM_001127461.3:c.2012G>C
NM_001127462.3:c.2012G>C
NM_001243133.2:c.2012G>CMANE SELECT
NM_004895.5:c.2018G>C
NM_183395.3:c.2012G>C
NP_001073289.2:p.Cys671Ser
NP_001120933.2:p.Cys671Ser
NP_001120934.2:p.Cys671Ser
NP_001230062.1:p.Cys671Ser
NP_004886.3:p.Cys673Ser
NP_004886.3:p.Cys673Ser
NP_899632.2:p.Cys671Ser
LRG_197t1:c.2018G>C
LRG_197:g.14289G>C
LRG_197p1:p.Cys673Ser
NC_000001.10:g.247588763G>C
NM_004895.4:c.2018G>C

Protein change:

C671S

Links:

dbSNP: rs199885115

NCBI 1000 Genomes Browser:

rs199885115

Molecular consequence:

NM_001079821.3:c.2012G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127461.3:c.2012G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127462.3:c.2012G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001243133.2:c.2012G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004895.5:c.2018G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_183395.3:c.2012G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

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Homo sapiens tRNA methyltransferase 61A (TRMT61A), mRNA
Homo sapiens tRNA methyltransferase 61A (TRMT61A), mRNA
gi|1519312525|ref|NM_152307.3|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000959128	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 27, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000959128

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 27, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000959128.4

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with NLRP3-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with serine at codon 673 of the NLRP3 protein (p.Cys673Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine.

#	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: Sep 29, 2024

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