NM_033629.6(TREX1):c.667G>A (p.Ala223Thr) AND not provided

Germline classification:: Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:: Dec 29, 2025
Review status:: criteria provided, conflicting classifications

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:: RCV000433529.6

Allele description [Variation Report for NM_033629.6(TREX1):c.667G>A (p.Ala223Thr)]

NM_033629.6(TREX1):c.667G>A (p.Ala223Thr)

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.667G>A (p.Ala223Thr)

Other names:

NM_016381.5:c.832G>A; NM_016381.3:c.832G>A

HGVS:

NC_000003.12:g.48467322G>A
NG_009820.2:g.6493G>A
NG_033100.1:g.38539C>T
NG_033100.2:g.42488C>T
NG_041782.1:g.25613G>A
NG_099340.1:g.383G>A
NM_001271022.2:c.*1768G>A
NM_001271023.2:c.*1768G>A
NM_007248.5:c.637G>A
NM_032166.4:c.*1768G>A
NM_033629.6:c.667G>AMANE SELECT
NM_130384.3:c.*1768G>AMANE SELECT
NP_009179.2:p.Ala213Thr
NP_338599.1:p.Ala223Thr
NP_338599.1:p.Ala223Thr
LRG_282t1:c.667G>A
LRG_282:g.6493G>A
LRG_282p1:p.Ala223Thr
NC_000003.11:g.48508721G>A
NM_033629.2:c.667G>A
NM_033629.3:c.667G>A
NM_033629.4:c.667G>A
NR_153405.1:n.3976G>A

Protein change:

A213T

Links:

dbSNP: rs766785968

Molecular consequence:

NM_001271022.2:c.*1768G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001271023.2:c.*1768G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_032166.4:c.*1768G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_130384.3:c.*1768G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_007248.5:c.637G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033629.6:c.667G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_153405.1:n.3976G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000521216	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Dec 29, 2025)	germline	clinical testing	Citation Link,
SCV004236930	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 22, 2023)	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

SCV000521216

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Dec 29, 2025)

germline

clinical testing

Citation Link,

SCV004236930

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 22, 2023)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	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 GeneDx, SCV000521216.5

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

Description

Reported in multiple patients with Aicardi-Goutieres syndrome with a second variant, however parental testing was not performed to determine whether the variants were in cis or trans (PMID: 24300241, 33053223); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31475890, 33053223, 34426522, 31589614, 37357214, Puckelwartz2023[casereport], 35879334, 34490982, 32877590, 25604658, 24300241, 38003924)

#	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 Revvity Omics, Revvity, SCV004236930.2

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

#	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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