NM_033629.6(TREX1):c.650G>A (p.Arg217Gln) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 27, 2024
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:
RCV002041257.4

Allele description [Variation Report for NM_033629.6(TREX1):c.650G>A (p.Arg217Gln)]

NM_033629.6(TREX1):c.650G>A (p.Arg217Gln)

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.650G>A (p.Arg217Gln)
HGVS:
  • NC_000003.12:g.48467305G>A
  • NG_009820.2:g.6476G>A
  • NG_033100.1:g.38556C>T
  • NG_033100.2:g.42505C>T
  • NG_041782.1:g.25596G>A
  • NG_099340.1:g.366G>A
  • NM_001271022.2:c.*1751G>A
  • NM_001271023.2:c.*1751G>A
  • NM_007248.5:c.620G>A
  • NM_032166.4:c.*1751G>A
  • NM_033629.6:c.650G>AMANE SELECT
  • NM_130384.3:c.*1751G>AMANE SELECT
  • NP_009179.2:p.Arg207Gln
  • NP_338599.1:p.Arg217Gln
  • NP_338599.1:p.Arg217Gln
  • LRG_282t1:c.650G>A
  • LRG_282:g.6476G>A
  • LRG_282p1:p.Arg217Gln
  • NC_000003.11:g.48508704G>A
  • NM_033629.4:c.650G>A
  • NR_153405.1:n.3959G>A
Protein change:
R207Q
Links:
dbSNP: rs775117062
NCBI 1000 Genomes Browser:
rs775117062
Molecular consequence:
  • NM_001271022.2:c.*1751G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001271023.2:c.*1751G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_032166.4:c.*1751G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_130384.3:c.*1751G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_007248.5:c.620G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033629.6:c.650G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_153405.1:n.3959G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV002310525Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jan 27, 2024) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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, SCV002310525.3

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

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 217 of the TREX1 protein (p.Arg217Gln). This variant is present in population databases (rs775117062, gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TREX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1518077). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

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

Last Updated: Sep 29, 2024