rs3135941

Variant names:

• chr3-48466268-T-A
• rs3135941
• NM_033629.6:c.-68T>A

Your query was ambiguous. Multiple possible variants found:

• chr3-48466268-T-A
• chr3-48466268-T-C
• chr3-48466268-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033629.6(TREX1):​c.-68T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000856 in 467,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000086 (0 hom.)
• Consequence: TREX1 NM_033629.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 25 publications found

Genes affected

TREX1 (HGNC:12269): (three prime repair exonuclease 1) This gene encodes a nuclear protein with 3' exonuclease activity. The encoded protein may play a role in DNA repair and serve as a proofreading function for DNA polymerase. Mutations in this gene result in Aicardi-Goutieres syndrome, chilblain lupus, Cree encephalitis, and other diseases of the immune system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012]

ATRIP (HGNC:33499): (ATR interacting protein) This gene encodes an essential component of the DNA damage checkpoint. The encoded protein binds to single-stranded DNA coated with replication protein A. The protein also interacts with the ataxia telangiectasia and Rad3 related protein kinase, resulting in its accumulation at intranuclear foci induced by DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2012]

ATRIP Gene-Disease associations (from GenCC):

• breast cancer

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• Seckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary breast carcinoma

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ATRIP-TREX1 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033629.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREX1	NM_033629.6	MANE Select	c.-68T>A		5_prime_UTR	Exon 1 of 2	NP_338599.1	Q9NSU2-3
	ATRIP	NM_130384.3	MANE Select	c.*714T>A		3_prime_UTR	Exon 13 of 13	NP_569055.1	Q8WXE1-1
	ATRIP	NM_032166.4		c.*714T>A		3_prime_UTR	Exon 12 of 12	NP_115542.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREX1	ENST00000625293.3	TSL:6 MANE Select	c.-68T>A		5_prime_UTR	Exon 1 of 2	ENSP00000486676.2	Q9NSU2-3
	TREX1	ENST00000433541.1	TSL:1	c.-387T>A		5_prime_UTR	Exon 2 of 4	ENSP00000412404.1	C9J052
	ATRIP	ENST00000320211.10	TSL:1 MANE Select	c.*714T>A		3_prime_UTR	Exon 13 of 13	ENSP00000323099.3	Q8WXE1-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000856 AC: 4 AN: 467492 Hom.: 0 Cov.: 5 AF XY: 0.0000122 AC XY: 3 AN XY: 245990

African (AFR) AF: 0.00 AC: 0 AN: 13200

American (AMR) AF: 0.00 AC: 0 AN: 22270

Ashkenazi Jewish (ASJ) AF: 0.0000710 AC: 1 AN: 14082

East Asian (EAS) AF: 0.00 AC: 0 AN: 30200

South Asian (SAS) AF: 0.00 AC: 0 AN: 47806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31800

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2014

European-Non Finnish (NFE) AF: 0.0000107 AC: 3 AN: 279566

Other (OTH) AF: 0.00 AC: 0 AN: 26554

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1488

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.43
DANN	Benign	0.68
PhyloP100		-1.4
PromoterAI		0.14	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3135941; hg19: chr3-48507667;