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NM_033629.6(TREX1):c.349C>T (p.Gln117Ter) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 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:
RCV003799082.1

Allele description [Variation Report for NM_033629.6(TREX1):c.349C>T (p.Gln117Ter)]

NM_033629.6(TREX1):c.349C>T (p.Gln117Ter)

Genes:
ATRIP:ATR interacting protein [Gene - OMIM - HGNC]
ATRIP-TREX1:ATRIP-TREX1 readthrough [Gene]
TREX1:three prime repair exonuclease 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p21.31
Genomic location:
Preferred name:
NM_033629.6(TREX1):c.349C>T (p.Gln117Ter)
HGVS:
  • NC_000003.12:g.48467004C>T
  • NG_009820.2:g.6175C>T
  • NG_033100.1:g.38857G>A
  • NG_033100.2:g.42806G>A
  • NG_041782.1:g.25295C>T
  • NG_099339.1:g.947C>T
  • NG_099340.1:g.65C>T
  • NM_001271022.2:c.*1450C>T
  • NM_001271023.2:c.*1450C>T
  • NM_007248.5:c.319C>T
  • NM_032166.4:c.*1450C>T
  • NM_033629.6:c.349C>TMANE SELECT
  • NM_130384.3:c.*1450C>TMANE SELECT
  • NP_009179.2:p.Gln107Ter
  • NP_338599.1:p.Gln117Ter
  • NP_338599.1:p.Gln117Ter
  • LRG_282t1:c.349C>T
  • LRG_282:g.6175C>T
  • LRG_282p1:p.Gln117Ter
  • NC_000003.11:g.48508403C>T
  • NM_033629.4:c.349C>T
  • NR_153405.1:n.3658C>T
Protein change:
Q107*
Molecular consequence:
  • NM_001271022.2:c.*1450C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001271023.2:c.*1450C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_032166.4:c.*1450C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_130384.3:c.*1450C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NR_153405.1:n.3658C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_007248.5:c.319C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_033629.6:c.349C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Aicardi-Goutieres syndrome 1
Synonyms:
CREE ENCEPHALITIS; ENCEPHALOPATHY, FAMILIAL INFANTILE, WITH INTRACRANIAL CALCIFICATION AND CHRONIC CEREBROSPINAL FLUID LYMPHOCYTOSIS; PSEUDOTOXOPLASMOSIS SYNDROME
Identifiers:
MONDO: MONDO:0009165; MedGen: C0796126; Orphanet: 51; OMIM: 225750
Name:
Chilblain lupus 1 (CHBL1)
Identifiers:
MONDO: MONDO:0012500; MedGen: C0024145; OMIM: 610448
Name:
Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCLS)
Synonyms:
Vasculopathy, retinal, with cerebral leukodystrophy; Cerebroretinal vasculopathy, hereditary; Retinopathy, vascular, with cerebral and renal involvement and Raynaud and migraine phenomena
Identifiers:
MONDO: MONDO:0008641; MedGen: C1860518; Orphanet: 3421; Orphanet: 63261; Orphanet: 71291; OMIM: 192315

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004583830Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 10, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus.

Crow YJ, Hayward BE, Parmar R, Robins P, Leitch A, Ali M, Black DN, van Bokhoven H, Brunner HG, Hamel BC, Corry PC, Cowan FM, Frints SG, Klepper J, Livingston JH, Lynch SA, Massey RF, Meritet JF, Michaud JL, Ponsot G, Voit T, Lebon P, et al.

Nat Genet. 2006 Aug;38(8):917-20. Epub 2006 Jul 16.

PubMed [citation]
PMID:
16845398

Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1.

Crow YJ, Chase DS, Lowenstein Schmidt J, Szynkiewicz M, Forte GM, Gornall HL, Oojageer A, Anderson B, Pizzino A, Helman G, Abdel-Hamid MS, Abdel-Salam GM, Ackroyd S, Aeby A, Agosta G, Albin C, Allon-Shalev S, Arellano M, Ariaudo G, Aswani V, Babul-Hirji R, Baildam EM, et al.

Am J Med Genet A. 2015 Feb;167A(2):296-312. doi: 10.1002/ajmg.a.36887. Epub 2015 Jan 16.

PubMed [citation]
PMID:
25604658
PMCID:
PMC4382202
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004583830.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Gln117*) in the TREX1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 198 amino acid(s) of the TREX1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TREX1-related conditions. This variant disrupts a region of the TREX1 protein in which other variant(s) (p.Arg164*) have been determined to be pathogenic (PMID: 16845398, 25604658). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 5, 2024