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NM_001065.4(TNFRSF1A):c.950_951insTG (p.Tyr318fs) AND TNF receptor-associated periodic fever syndrome (TRAPS)

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Dec 14, 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:
RCV003477446.2

Allele description [Variation Report for NM_001065.4(TNFRSF1A):c.950_951insTG (p.Tyr318fs)]

NM_001065.4(TNFRSF1A):c.950_951insTG (p.Tyr318fs)

Gene:
TNFRSF1A:TNF receptor superfamily member 1A [Gene - OMIM - HGNC]
Variant type:
Insertion
Cytogenetic location:
12p13.31
Genomic location:
Preferred name:
NM_001065.4(TNFRSF1A):c.950_951insTG (p.Tyr318fs)
HGVS:
  • NC_000012.12:g.6329884_6329885insCA
  • NG_007506.1:g.17211_17212insTG
  • NM_001065.4:c.950_951insTGMANE SELECT
  • NM_001346091.2:c.626_627insTG
  • NM_001346092.2:c.491_492insTG
  • NP_001056.1:p.Tyr318Alafs
  • NP_001056.1:p.Tyr318fs
  • NP_001333020.1:p.Tyr210fs
  • NP_001333021.1:p.Tyr165fs
  • LRG_193t1:c.950_951insTG
  • LRG_193:g.17211_17212insTG
  • LRG_193p1:p.Tyr318Alafs
  • NC_000012.11:g.6439050_6439051insCA
  • NM_001065.3:c.950_951insTG
  • NR_144351.2:n.1138_1139insTG
Protein change:
Y165fs
Molecular consequence:
  • NM_001065.4:c.950_951insTG - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001346091.2:c.626_627insTG - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001346092.2:c.491_492insTG - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_144351.2:n.1138_1139insTG - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004218545Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Dec 14, 2023) 		unknownclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen, SCV004218545.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
11not providednot providedclinical testing PubMed (1)

Description

The detected change is not reported in the general population (gnomAD) (as of December 14, 2023). It has not yet been described in the ClinVar database or in the literature. The variant represents a frame shift with a subsequent stop codon. This usually leads to either premature termination of translation or a so-called “nonsense-mediated mRNA decay” (NMD). In this case, the present 2 bp insertion leads to a shift in the reading frame with the consequence of a premature stop codon in direct proximity to the 3' end of the penultimate exon. Premature stop codons less than 50 bp before the end of the penultimate exon often escape the NMD, which can lead to the formation of a truncated protein. Taking into account that so far only missense variants in TNFRSF1A have been described as pathogenic and that loss-of-function variants therefore probably do not fit the suspected pathomechanism, it is highly likely that the detected change is likely pathogenetic due to the resulting, presumably C-terminally shortened protein. The variant is currently considered a “likely pathogenic variant” (ACMG criteria).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Jun 23, 2024