NM_033629.6(TREX1):c.58dup (p.Glu20fs) AND TREX1-related disorder

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 28, 2020
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:: RCV001731376.4

Allele description [Variation Report for NM_033629.6(TREX1):c.58dup (p.Glu20fs)]

NM_033629.6(TREX1):c.58dup (p.Glu20fs)

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:

Duplication

Cytogenetic location:

3p21.31

Genomic location:

Preferred name:

NM_033629.6(TREX1):c.58dup (p.Glu20fs)

Other names:

NM_033629.6(TREX1):c.58dup; p.Glu20fs

HGVS:

NC_000003.12:g.48466713dup
NG_009820.2:g.5884dup
NG_033100.1:g.39149dup
NG_033100.2:g.43098dup
NG_041782.1:g.25004dup
NG_099339.1:g.656dup
NM_001271022.2:c.*1159dup
NM_001271023.2:c.*1159dup
NM_007248.5:c.28dup
NM_032166.4:c.*1159dup
NM_033629.6:c.58dupMANE SELECT
NM_130384.3:c.*1159dupMANE SELECT
NP_009179.2:p.Glu10fs
NP_338599.1:p.Glu20Glyfs
NP_338599.1:p.Glu20fs
LRG_282t1:c.58dup
AAK07616.1:p.Glu20GlyfsTer81
AF319569.1:c.58_59insG
LRG_282:g.5884dup
LRG_282p1:p.Glu20fs
NC_000003.11:g.48508110_48508111insG
NC_000003.11:g.48508112dup
NM_007248.3:c.28dup
NM_007248.5:c.26_27insG
NM_033629.2:c.58dup
NM_033629.3:c.58dup
NM_033629.4:c.58dup
NM_033629.4:c.58dupG
NR_153405.1:n.3367dup

Protein change:

E10fs

Links:

dbSNP: rs78300695

Molecular consequence:

NM_001271022.2:c.*1159dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001271023.2:c.*1159dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_032166.4:c.*1159dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_130384.3:c.*1159dup - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_007248.5:c.28dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_033629.6:c.58dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_153405.1:n.3367dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: TREX1-related disorder
Synonyms:: TREX1-related condition; TREX1-related disorders
Identifiers:: MedGen: CN239414

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001984797	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 28, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004725028	PreventionGenetics, part of Exact Sciences	no assertion criteria provided	Pathogenic (Aug 27, 2024)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001984797

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 28, 2020)

germline

clinical testing

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

SCV004725028

PreventionGenetics, part of Exact Sciences

no assertion criteria provided

Pathogenic
(Aug 27, 2024)

germline

clinical testing

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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical 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 Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV001984797.1

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

Description

This frameshift variant is found in the only exon of TREX1, and frameshift variants located downstream of this variant have been reported as disease-causing variants in the Human Gene Mutation Database (PMID: 24183309, 20301648). This variant has been previously reported as a compound heterozygous and a homozygous change in patients with Aicardi-Goutieres syndrome (PMID: 16845398, 26182405, 28832562, 29453417). It is present in the heterozygous state in the gnomAD population database at a frequency of .013% (32/251392) and thus is presumed to be rare. Based on the available evidence, the c.28dup (p.Glu10GlyfsTer82) variant is classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From PreventionGenetics, part of Exact Sciences, SCV004725028.2

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

Description

The TREX1 c.58dupG variant is predicted to result in a frameshift and premature protein termination (p.Glu20Glyfs*82). This variant (aka c.223dup, p.Glu75Glyfs*82) has been reported in the homozygous or compound heterozygous states in multiple individuals with Aicardi-Goutières syndrome (Crow et al. 2006. PubMed ID: 16845398; Crow et al. 2015. PubMed ID: 25604658. Table S1; Lim et al. 2015. PubMed ID: 26182405. Supplementary file 1; Dillon et al. 2018. PubMed ID: 29453417. Table S1). This variant is reported in 0.10% of alleles in individuals of South Asian descent in gnomAD. Frameshift variants in TREX1 are expected to be pathogenic. This variant is interpreted as pathogenic.

#	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: Jul 6, 2026

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