X-153444789-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080701.4(TREX2):​c.642G>C​(p.Glu214Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000923 in 1,083,186 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E214E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: TREX2 NM_080701.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06826565).

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>C	p.Glu214Asp	missense	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>C	p.Glu214Asp	missense	Exon 2 of 2	ENSP00000359251.2	Q9BQ50-2
	TREX2	ENST00000334497.7	TSL:1	c.771G>C	p.Glu257Asp	missense	Exon 11 of 11	ENSP00000334993.2	Q9BQ50-1
	TREX2	ENST00000370232.4	TSL:1	c.771G>C	p.Glu257Asp	missense	Exon 11 of 11	ENSP00000359252.1	Q9BQ50-1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 9.23e-7 AC: 1 AN: 1083186 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 353984

African (AFR) AF: 0.00 AC: 0 AN: 26305

American (AMR) AF: 0.00 AC: 0 AN: 32571

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 38508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3961

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 835819

Other (OTH) AF: 0.0000219 AC: 1 AN: 45577

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.12	T
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	M
PhyloP100		0.60
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.045
Sift	Benign	0.38	T
Sift4G	Benign	0.54	T
Polyphen		0.011	B
Vest4		0.081
MutPred		0.30		Gain of helix (P = 0.0349)
MVP		0.17
MPC		0.023
ClinPred		0.052	T
GERP RS		2.6
Varity_R		0.31
gMVP		0.53
Mutation Taster		=93/7	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;