X-153445171-C-G

Variant names:

• chrX-153445171-C-G
• NM_080701.4:c.260G>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.260G>C​(p.Arg87Pro) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: TREX2 NM_080701.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.41

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=0.19987747).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TREX2	NM_080701.4	c.260G>C	p.Arg87Pro	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.260G>C	p.Arg87Pro	missense_variant	Exon 2 of 2	5	NM_080701.4	ENSP00000359251.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.260G>C (p.R87P) alteration is located in exon 2 (coding exon 1) of the TREX2 gene. This alteration results from a G to C substitution at nucleotide position 260, causing the arginine (R) at amino acid position 87 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6
DANN	Benign	0.89
DEOGEN2	Benign	0.19	.;.;T;.;.;T;T
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.64	T;.;T;.;.;.;.
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	.;.;L;.;.;L;L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N;N;.;N;N;N;N
REVEL	Benign	0.044
Sift	Benign	0.27	T;T;.;T;T;T;T
Sift4G	Benign	0.32	T;T;T;T;T;T;T
Polyphen		0.52	.;.;P;.;.;P;P
Vest4		0.29
MutPred		0.48		.;.;Loss of solvent accessibility (P = 0.0045);.;.;Loss of solvent accessibility (P = 0.0045);Loss of solvent accessibility (P = 0.0045);
MVP		0.085
MPC		0.074
ClinPred		0.40	T
GERP RS		-3.3
Varity_R		0.49
gMVP		0.67

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-152710629;