chrX-153444789-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/20 in silico tools predict 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: 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TREX2	NM_080701.4	c.642G>C	p.Glu214Asp	missense_variant	Exon 2 of 2	ENST00000370231.3	NP_542432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TREX2	ENST00000370231.3	c.642G>C	p.Glu214Asp	missense_variant	Exon 2 of 2	5	NM_080701.4	ENSP00000359251.2

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000219

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;.;T;T
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.63	T;.;T;.;.;.;.
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.068	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;.;M;.;.;M;M
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.1	N;N;.;N;N;N;N
REVEL	Benign	0.045
Sift	Benign	0.38	T;T;.;T;T;T;T
Sift4G	Benign	0.54	T;T;T;T;T;T;T
Polyphen		0.011	.;.;B;.;.;B;B
Vest4		0.081
MutPred		0.30		.;.;Gain of helix (P = 0.0349);.;.;Gain of helix (P = 0.0349);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-152710247;