NM_001065.4(TNFRSF1A):c.259G>A (p.Gly87Ser) AND TNF receptor-associated periodic fever syndrome (TRAPS)

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 10, 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:: RCV003513621.1

Allele description

NM_001065.4(TNFRSF1A):c.259G>A (p.Gly87Ser)

Gene:

TNFRSF1A:TNF receptor superfamily member 1A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12p13.31

Genomic location:

Preferred name:

NM_001065.4(TNFRSF1A):c.259G>A (p.Gly87Ser)

HGVS:

NC_000012.12:g.6333800C>T
NG_007506.1:g.13296G>A
NM_001065.4:c.259G>AMANE SELECT
NM_001346091.2:c.-66G>A
NM_001346092.2:c.-319G>A
NP_001056.1:p.Gly87Ser
NP_001056.1:p.Gly87Ser
LRG_193t1:c.259G>A
LRG_193:g.13296G>A
LRG_193p1:p.Gly87Ser
NC_000012.11:g.6442966C>T
NM_001065.3:c.259G>A
NR_144351.2:n.521G>A

Protein change:

G87S

Molecular consequence:

NM_001346091.2:c.-66G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001346092.2:c.-319G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001065.4:c.259G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_144351.2:n.521G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: TNF receptor-associated periodic fever syndrome (TRAPS) (FPF)
Synonyms:: Familial Hibernian fever; Tumor necrosis factor receptor-associated periodic syndrome; TNF receptor-associated periodic syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007727; MedGen: C1275126; Orphanet: 32960; OMIM: 142680

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004295825	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 10, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22566169, 31429073, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004295825

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 10, 2023)

germline

clinical testing

PubMed (3)
[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

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

Functional analysis of a novel G87V TNFRSF1A mutation in patients with TNF receptor-associated periodic syndrome.

Tsuji S, Matsuzaki H, Iseki M, Nagasu A, Hirano H, Ishihara K, Ueda N, Honda Y, Horiuchi T, Nishikomori R, Morita Y, Mukai T.

Clin Exp Immunol. 2019 Dec;198(3):416-429. doi: 10.1111/cei.13365. Epub 2019 Sep 4.

PubMed [citation]

PMID:: 31429073
PMCID:: PMC6857086

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004295825.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 87 of the TNFRSF1A protein (p.Gly87Ser). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with clinical features of TNF receptor-associated periodic fever syndrome (PMID: 22566169). 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) performed at Invitae indicates that this missense variant is expected to disrupt TNFRSF1A protein function. This variant disrupts the p.Gly87 amino acid residue in TNFRSF1A. Other variant(s) that disrupt this residue have been observed in individuals with TNFRSF1A-related conditions (PMID: 31429073), which suggests that this may be a clinically significant amino acid residue. 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.

#	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: Feb 20, 2024

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