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NM_001243133.2(NLRP3):c.1639A>T (p.Ser547Cys)

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Interpretation:
Conflicting interpretations of pathogenicity​

Benign(1);Likely benign(2);Uncertain significance(2)

Review status:
criteria provided, conflicting interpretations
Submissions:
5 (Most recent: Oct 30, 2021)
Last evaluated:
Oct 7, 2021
Accession:
VCV000536887.10
Variation ID:
536887
Description:
single nucleotide variant
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NM_001243133.2(NLRP3):c.1639A>T (p.Ser547Cys)

Allele ID
515874
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
1q44
Genomic location
1: 247425088 (GRCh38) GRCh38 UCSC
1: 247588390 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_004895.5:c.1645A>T NP_004886.3:p.Ser549Cys missense
NM_183395.3:c.1639A>T NP_899632.2:p.Ser547Cys missense
NC_000001.10:g.247588390A>T
... more HGVS
Protein change
S549C, S547C
Other names
-
Canonical SPDI
NC_000001.11:247425087:A:T
Functional consequence
-
Global minor allele frequency (GMAF)
0.00060 (T)

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00107
Trans-Omics for Precision Medicine (TOPMed) 0.00124
The Genome Aggregation Database (gnomAD), exomes 0.00028
1000 Genomes Project 0.00060
Exome Aggregation Consortium (ExAC) 0.00037
The Genome Aggregation Database (gnomAD) 0.00061
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00108
Links
ClinGen: CA1495048
dbSNP: rs139833874
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Dec 3, 2018 RCV000768276.1
Likely benign 1 criteria provided, single submitter Jan 16, 2019 RCV000825794.1
Likely benign 1 criteria provided, single submitter Nov 2, 2020 RCV001088695.2
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Oct 7, 2021 RCV000645590.7
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
NLRP3 - - GRCh38
GRCh37
521 603

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Dec 03, 2018)
criteria provided, single submitter
Method: clinical testing
Chronic infantile neurological, cutaneous and articular syndrome
Familial cold autoinflammatory syndrome 1
Familial amyloid nephropathy with urticaria AND deafness
Allele origin: germline
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Accession: SCV000898854.1
Submitted: (Dec 12, 2018)
Evidence details
Comment:
NLRP3 NM_004895.4 exon 4 p.Ser549Cys (c.1645A>T): This variant has not been reported in the literature and is present in 0.3% (81/24950) of African alleles in … (more)
Likely benign
(Jan 16, 2019)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000967263.1
Submitted: (Mar 21, 2019)
Evidence details
Comment:
The p.Ser549Cys variant in NLRP3 is classified as likely benign because it has b een identified in 0.3% (81/24950) of African chromosomes by gnomAD (http://gnoma … (more)
Benign
(Mar 21, 2019)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Athena Diagnostics Inc
Accession: SCV001144769.1
Submitted: (Sep 25, 2019)
Evidence details
Likely benign
(Nov 02, 2020)
criteria provided, single submitter
Method: clinical testing
Cryopyrin associated periodic syndrome
Allele origin: germline
Invitae
Accession: SCV000767340.4
Submitted: (Jan 07, 2021)
Evidence details
Uncertain significance
(Oct 07, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001767111.2
Submitted: (Oct 30, 2021)
Evidence details
Comment:
Observed in two patients with NLRP3-related disorders in the published literature (Lane et al., 2015; Brighouse et al., 2018); In silico analysis supports that this … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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There are no citations in ClinVar for this variation. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs139833874...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 27, 2021