NM_080701.4:c.642G>A

Variant names:

• chrX-153444789-C-T
• rs145170280
• NM_080701.4:c.642G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_080701.4(TREX2):​c.642G>A​(p.Glu214Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000491 in 1,196,533 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 157 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., 7 hem., cov: 25)
  • Exomes 𝑓: 0.00051 (0 hom. 150 hem.)
• Consequence: TREX2 NM_080701.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.599
• Publications: 0 publications found

Genes affected

TREX2 (HGNC:12270): (three prime repair exonuclease 2) This gene encodes a nuclear protein with 3' to 5' exonuclease activity. The encoded protein participates in double-stranded DNA break repair, and may interact with DNA polymerase delta. [provided by RefSeq, Nov 2012]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-153444789-C-T is Benign according to our data. Variant chrX-153444789-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2661684.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.599 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080701.4. 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
	TREX2	NM_080701.4	MANE Select	c.642G>A	p.Glu214Glu	synonymous	Exon 2 of 2	NP_542432.2	Q9BQ50-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TREX2	ENST00000370231.3	TSL:5 MANE Select	c.642G>A	p.Glu214Glu	synonymous	Exon 2 of 2	ENSP00000359251.2	Q9BQ50-2
	TREX2	ENST00000334497.7	TSL:1	c.771G>A	p.Glu257Glu	synonymous	Exon 11 of 11	ENSP00000334993.2	Q9BQ50-1
	TREX2	ENST00000370232.4	TSL:1	c.771G>A	p.Glu257Glu	synonymous	Exon 11 of 11	ENSP00000359252.1	Q9BQ50-1

Frequencies

GnomAD3 genomes AF: 0.000318 AC: 36 AN: 113347 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000640

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000918

Gnomad ASJ AF: 0.000752

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000314

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000525

Gnomad OTH AF: 0.000652

GnomAD2 exomes AF: 0.000336 AC: 49 AN: 145800 AF XY: 0.000304

Gnomad AFR exome AF: 0.000101

Gnomad AMR exome AF: 0.0000421

Gnomad ASJ exome AF: 0.000602

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000688

Gnomad OTH exome AF: 0.000262

GnomAD4 exome AF: 0.000510 AC: 552 AN: 1083186 Hom.: 0 Cov.: 31 AF XY: 0.000424 AC XY: 150 AN XY: 353984

African (AFR) AF: 0.000114 AC: 3 AN: 26305

American (AMR) AF: 0.0000614 AC: 2 AN: 32571

Ashkenazi Jewish (ASJ) AF: 0.000790 AC: 15 AN: 18985

East Asian (EAS) AF: 0.00 AC: 0 AN: 29647

South Asian (SAS) AF: 0.00 AC: 0 AN: 51813

European-Finnish (FIN) AF: 0.0000779 AC: 3 AN: 38508

Middle Eastern (MID) AF: 0.000252 AC: 1 AN: 3961

European-Non Finnish (NFE) AF: 0.000603 AC: 504 AN: 835819

Other (OTH) AF: 0.000527 AC: 24 AN: 45577

GnomAD4 genome AF: 0.000318 AC: 36 AN: 113347 Hom.: 0 Cov.: 25 AF XY: 0.000197 AC XY: 7 AN XY: 35479

African (AFR) AF: 0.0000640 AC: 2 AN: 31256

American (AMR) AF: 0.0000918 AC: 1 AN: 10898

Ashkenazi Jewish (ASJ) AF: 0.000752 AC: 2 AN: 2659

East Asian (EAS) AF: 0.00 AC: 0 AN: 3565

South Asian (SAS) AF: 0.00 AC: 0 AN: 2805

European-Finnish (FIN) AF: 0.000314 AC: 2 AN: 6372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.000525 AC: 28 AN: 53334

Other (OTH) AF: 0.000652 AC: 1 AN: 1533

Alfa AF: 0.000912 Hom.: 8

Bravo AF: 0.000329

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.6
DANN	Benign	0.73
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism

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: rs145170280; hg19: chrX-152710247;