rs781867557

Variant names:

• chrX-153444824-G-A
• rs781867557
• NM_080701.4:c.607C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_080701.4(TREX2):​c.607C>T​(p.His203Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000075 in 1,200,056 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.0000088 (0 hom., 0 hem., cov: 25)
  • Exomes 𝑓: 0.0000074 (0 hom. 4 hem.)
• Consequence: TREX2 NM_080701.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.20
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08718556).
• BS2: High Hemizygotes in GnomAdExome4 at 4 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.607C>T	p.His203Tyr	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.607C>T	p.His203Tyr	missense	Exon 2 of 2	ENSP00000359251.2	Q9BQ50-2
	TREX2	ENST00000334497.7	TSL:1	c.736C>T	p.His246Tyr	missense	Exon 11 of 11	ENSP00000334993.2	Q9BQ50-1
	TREX2	ENST00000370232.4	TSL:1	c.736C>T	p.His246Tyr	missense	Exon 11 of 11	ENSP00000359252.1	Q9BQ50-1

Frequencies

GnomAD3 genomes AF: 0.00000883 AC: 1 AN: 113257 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000395 AC: 6 AN: 151894 AF XY: 0.0000828

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000332

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000311

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000736 AC: 8 AN: 1086799 Hom.: 0 Cov.: 31 AF XY: 0.0000112 AC XY: 4 AN XY: 355977

African (AFR) AF: 0.00 AC: 0 AN: 26340

American (AMR) AF: 0.00 AC: 0 AN: 33461

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19081

East Asian (EAS) AF: 0.000168 AC: 5 AN: 29772

South Asian (SAS) AF: 0.00 AC: 0 AN: 52169

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38759

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4073

European-Non Finnish (NFE) AF: 0.00000239 AC: 2 AN: 837466

Other (OTH) AF: 0.0000219 AC: 1 AN: 45678

GnomAD4 genome AF: 0.00000883 AC: 1 AN: 113257 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 35405

African (AFR) AF: 0.00 AC: 0 AN: 31238

American (AMR) AF: 0.00 AC: 0 AN: 10885

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2656

East Asian (EAS) AF: 0.00 AC: 0 AN: 3557

South Asian (SAS) AF: 0.00 AC: 0 AN: 2806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6361

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53299

Other (OTH) AF: 0.00 AC: 0 AN: 1533

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000333 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Intellectual disability (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.83
DEOGEN2	Benign	0.060	T
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.2
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.057	B
Vest4		0.23
MutPred		0.52		Gain of catalytic residue at L241 (P = 0.0578)
MVP		0.14
MPC		0.024
ClinPred		0.058	T
GERP RS		4.9
Varity_R		0.16
gMVP		0.48
Mutation Taster		=97/3	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: rs781867557; hg19: chrX-152710282;