chrX-153445165-C-A

Variant names:

• chrX-153445165-C-A
• rs373809426
• NM_080701.4:c.266G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080701.4(TREX2):​c.266G>T​(p.Arg89Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 24)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: TREX2 NM_080701.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201

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=0.1724135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TREX2	NM_080701.4	c.266G>T	p.Arg89Leu	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.266G>T	p.Arg89Leu	missense_variant	Exon 2 of 2	5	NM_080701.4	ENSP00000359251.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1094569 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 360883

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: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.93
DEOGEN2	Benign	0.21	.;.;T;.;.;T;T
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.71	T;.;T;.;.;.;.
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.17	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	.;.;L;.;.;L;L
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.3	N;N;.;N;N;N;N
REVEL	Benign	0.061
Sift	Benign	0.15	T;T;.;T;T;T;T
Sift4G	Benign	0.60	T;T;T;T;T;T;T
Polyphen		0.27	.;.;B;.;.;B;B
Vest4		0.28
MutPred		0.63		.;.;Gain of loop (P = 0.0013);.;.;Gain of loop (P = 0.0013);Gain of loop (P = 0.0013);
MVP		0.11
MPC		0.032
ClinPred		0.13	T
GERP RS		2.8
Varity_R		0.29
gMVP		0.39

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

LitVar

Other links and lift over

dbSNP: rs373809426; hg19: chrX-152710623;