3-48466285-ACTGCCTGC-ACTGCCTGCCTGC

Variant names:

• chr3-48466285-A-ACTGC
• rs371036312
• NM_033629.6:c.-34_-31dupCTGC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_033629.6(TREX1):​c.-34_-31dupCTGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000602 in 668,030 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00030 (0 hom.)
• Consequence: TREX1 NM_033629.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.630

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-TREX1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00162 (246/152250) while in subpopulation AFR AF= 0.00515 (214/41562). AF 95% confidence interval is 0.00458. There are 0 homozygotes in gnomad4. There are 114 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TREX1	NM_033629.6	c.-34_-31dupCTGC		5_prime_UTR_variant	Exon 1 of 2	ENST00000625293.3	NP_338599.1
ATRIP	NM_130384.3	c.*748_*751dupCTGC		3_prime_UTR_variant	Exon 13 of 13	ENST00000320211.10	NP_569055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TREX1	ENST00000625293	c.-34_-31dupCTGC		5_prime_UTR_variant	Exon 1 of 2		NM_033629.6	ENSP00000486676.2
ATRIP	ENST00000320211.10	c.*748_*751dupCTGC		3_prime_UTR_variant	Exon 13 of 13	1	NM_130384.3	ENSP00000323099.3

Frequencies

GnomAD3 genomes AF: 0.00162 AC: 246 AN: 152132 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00516

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.000302 AC: 156 AN: 515780 Hom.: 0 Cov.: 6 AF XY: 0.000258 AC XY: 70 AN XY: 271820

Gnomad4 AFR exome AF: 0.00512

Gnomad4 AMR exome AF: 0.000653

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000224

Gnomad4 SAS exome AF: 0.0000192

Gnomad4 FIN exome AF: 0.0000556

Gnomad4 NFE exome AF: 0.000110

Gnomad4 OTH exome AF: 0.000567

GnomAD4 genome AF: 0.00162 AC: 246 AN: 152250 Hom.: 0 Cov.: 33 AF XY: 0.00153 AC XY: 114 AN XY: 74452

Gnomad4 AFR AF: 0.00515

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs371036312; hg19: chr3-48507684;