NM_033629.6(TREX1):c.393C>G (p.Phe131Leu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 21, 2022
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:: RCV001867827.3

Allele description [Variation Report for NM_033629.6(TREX1):c.393C>G (p.Phe131Leu)]

NM_033629.6(TREX1):c.393C>G (p.Phe131Leu)

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.393C>G (p.Phe131Leu)

HGVS:

NC_000003.12:g.48467048C>G
NG_009820.2:g.6219C>G
NG_033100.1:g.38813G>C
NG_033100.2:g.42762G>C
NG_041782.1:g.25339C>G
NG_099339.1:g.991C>G
NG_099340.1:g.109C>G
NM_001271022.2:c.*1494C>G
NM_001271023.2:c.*1494C>G
NM_007248.5:c.363C>G
NM_032166.4:c.*1494C>G
NM_033629.6:c.393C>GMANE SELECT
NM_130384.3:c.*1494C>GMANE SELECT
NP_009179.2:p.Phe121Leu
NP_338599.1:p.Phe131Leu
NP_338599.1:p.Phe131Leu
LRG_282t1:c.393C>G
LRG_282:g.6219C>G
LRG_282p1:p.Phe131Leu
NC_000003.11:g.48508447C>G
NM_033629.4:c.393C>G
NR_153405.1:n.3702C>G

Protein change:

F121L

Links:

dbSNP: rs749667732

NCBI 1000 Genomes Browser:

rs749667732

Molecular consequence:

NM_001271022.2:c.*1494C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001271023.2:c.*1494C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_032166.4:c.*1494C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_130384.3:c.*1494C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_007248.5:c.363C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_033629.6:c.393C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_153405.1:n.3702C>G - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002132449	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 21, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002132449

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 21, 2022)

germline

clinical testing

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

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

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, SCV002132449.2

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

Description

This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 131 of the TREX1 protein (p.Phe131Leu). This variant is present in population databases (rs749667732, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TREX1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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: Sep 29, 2024

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