ENST00000625293:c.-38_-31delCTGCCTGC

Variant names:

• chr3-48466285-ACTGCCTGC-A
• rs371036312
• NM_033629.6:c.-38_-31delCTGCCTGC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000625293.3(TREX1):​c.-38_-31delCTGCCTGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 668,026 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (2 hom.)
• Consequence: TREX1 ENST00000625293.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48
• Publications: 0 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00188 (286/152250) while in subpopulation AMR AF = 0.00373 (57/15298). AF 95% confidence interval is 0.00295. There are 1 homozygotes in GnomAd4. There are 154 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR,AD,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000625293.3. 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.-38_-31delCTGCCTGC		5_prime_UTR	Exon 1 of 2	NP_338599.1	Q9NSU2-3
	ATRIP	NM_130384.3	MANE Select	c.*744_*751delCTGCCTGC		3_prime_UTR	Exon 13 of 13	NP_569055.1	Q8WXE1-1
	ATRIP	NM_032166.4		c.*744_*751delCTGCCTGC		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.-38_-31delCTGCCTGC		5_prime_UTR	Exon 1 of 2	ENSP00000486676.2	Q9NSU2-3
	TREX1	ENST00000433541.1	TSL:1	c.-357_-350delCTGCCTGC		5_prime_UTR	Exon 2 of 4	ENSP00000412404.1	C9J052
	ATRIP	ENST00000320211.10	TSL:1 MANE Select	c.*744_*751delCTGCCTGC		3_prime_UTR	Exon 13 of 13	ENSP00000323099.3	Q8WXE1-1

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 286 AN: 152132 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00240

Gnomad OTH AF: 0.000956

GnomAD4 exome AF: 0.00227 AC: 1173 AN: 515776 Hom.: 2 AF XY: 0.00234 AC XY: 637 AN XY: 271818

African (AFR) AF: 0.000337 AC: 5 AN: 14854

American (AMR) AF: 0.00189 AC: 52 AN: 27564

Ashkenazi Jewish (ASJ) AF: 0.00104 AC: 16 AN: 15428

East Asian (EAS) AF: 0.00 AC: 0 AN: 31316

South Asian (SAS) AF: 0.00320 AC: 167 AN: 52168

European-Finnish (FIN) AF: 0.00348 AC: 125 AN: 35944

Middle Eastern (MID) AF: 0.00503 AC: 11 AN: 2186

European-Non Finnish (NFE) AF: 0.00230 AC: 709 AN: 308090

Other (OTH) AF: 0.00312 AC: 88 AN: 28226

GnomAD4 genome AF: 0.00188 AC: 286 AN: 152250 Hom.: 1 Cov.: 33 AF XY: 0.00207 AC XY: 154 AN XY: 74452

African (AFR) AF: 0.000385 AC: 16 AN: 41562

American (AMR) AF: 0.00373 AC: 57 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5168

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4824

European-Finnish (FIN) AF: 0.00273 AC: 29 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00240 AC: 163 AN: 67998

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.0000542 Hom.: 0

Bravo AF: 0.00154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5
Mutation Taster		=292/8	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs371036312; hg19: chr3-48507684;