VCV000209199.8 - ClinVar

NM_033629.6(TREX1):c.212_213del (p.Val71fs)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (2)

2 out of 2 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_033629.6(TREX1):c.212_213del (p.Val71fs)

Variation ID: 209199 Accession: VCV000209199.8

Type and length

Microsatellite, 2 bp

Location

Cytogenetic: 3p21.31 3: 48466861-48466862 (GRCh38) [ NCBI UCSC ] 3: 48508260-48508261 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Sep 29, 2015	Feb 23, 2026	Oct 14, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_033629.6:c.212_213del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_338599.1:p.Val71fs	frameshift
NM_130384.3:c.*1307TG[3] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		3 prime UTR
NM_001271022.2:c.*1307TG[3]		3 prime UTR
NM_001271023.2:c.*1307TG[3]		3 prime UTR
NM_007248.5:c.182_183del	NP_009179.2:p.Val61fs	frameshift
NM_032166.4:c.*1307TG[3]		3 prime UTR
NR_153405.1:n.3515TG[3]		non-coding transcript variant
NC_000003.12:g.48466861TG[3]
NC_000003.11:g.48508260TG[3]
NG_009820.2:g.6032TG[3]
NG_033100.1:g.38993CA[3]
NG_033100.2:g.42942CA[3]
NG_041782.1:g.25152TG[3]
NG_099339.1:g.804TG[3]
LRG_282:g.6032TG[3]
LRG_282t1:c.212_213del	LRG_282p1:p.Val71fs

... more HGVS ... less HGVS

Protein change

V61fs, V71fs

Other names

Canonical SPDI

NC_000003.12:48466860:TGTGTGTG:TGTGTG

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA276178 dbSNP: rs74689946 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
ATRIP		-	-	GRCh38 GRCh37	1	1940
ATRIP-TREX1	-	-	-	GRCh38	-	1923
TREX1		-	-	GRCh38 GRCh37	4	631

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Aicardi-Goutieres syndrome 1	Pathogenic (1)	criteria provided, single submitter	Jul 15, 2014	RCV000191137.2
Aicardi-Goutieres syndrome 1 Chilblain lupus 1 Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations	Pathogenic (1)	criteria provided, single submitter	Oct 14, 2023	RCV001857681.6

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jul 15, 2014) C Contributing to aggregate classification	criteria provided, single submitter (Yang et al. 2013)	Aicardi Goutieres syndrome 1 (Autosomal recessive inheritance)	Baylor Genetics Study: Adult_WES Accession: SCV000245546.2 First in ClinVar: Sep 29, 2015 Last updated: Apr 13, 2025	Publications: PubMed (1) PubMed: 26633545 Comment: show This frameshift variant is categorized as deleterious according to ACMG guidelines (PMID:18414213) and was found once in our laboratory in trans with a missense variant [R114C] in an 18-year-old male with delayed development, neurologic regression, mineral deposition in the brain, adult-onset vision loss, inability to stand or walk, dystonia, abnormal teeth, maculopapular rash. (less) Observation: 1 Collection method: clinical testing Allele origin: maternal Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: maternal Affected status: yes Number of individuals with the variant: 1 Zygosity: 0 Homozygote, 0 Single Heterozygote, 1 Compound Heterozygote Age: 10-19 years Sex: male Platform type: Next-gen sequencing

Pathogenic (Oct 14, 2023) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations Aicardi-Goutieres syndrome 1 Chilblain lupus 1 Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002144057.5 First in ClinVar: Mar 28, 2022 Last updated: Feb 23, 2026	Publications: PubMed (2) PubMed: 16845398‚ 25604658 Comment: show This sequence change creates a premature translational stop signal (p.Val71Glyfs30) in the TREX1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 244 amino acid(s) of the TREX1 protein. This variant is present in population databases (rs797045073, gnomAD 0.02%). 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. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

This frameshift variant is categorized as deleterious according to ACMG guidelines (PMID:18414213) and was found once in our laboratory in trans with a missense variant [R114C] in an 18-year-old male with delayed development, neurologic regression, mineral deposition in the brain, adult-onset vision loss, inability to stand or walk, dystonia, abnormal teeth, maculopapular rash.

Comment:

This sequence change creates a premature translational stop signal (p.Val71Glyfs*30) in the TREX1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 244 amino acid(s) of the TREX1 protein. This variant is present in population databases (rs797045073, gnomAD 0.02%). 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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Molecular diagnostic experience of whole-exome sequencing in adult patients.	Posey JE	Genetics in medicine : official journal of the American College of Medical Genetics	2016	PMID: 26633545
Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1.	Crow YJ	American journal of medical genetics. Part A	2015	PMID: 25604658
Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus.	Crow YJ	Nature genetics	2006	PMID: 16845398

Text-mined citations for rs74689946 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jul 06, 2026