Genetic Variant TREX2:p.Pro149Gln (chrX-153444985-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080701.4(TREX2):c.446C>A(p.Pro149Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,064,681 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P149L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 25)

Exomes 𝑓: 0.0000019 ( 0 hom. 0 hem. )

Consequence

TREX2
NM_080701.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.250

Publications

0 publications found

Variant links:

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]

TREX2 links:

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ACMG classification

Classification was made for transcript

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=0.10233897).

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.446C>A	p.Pro149Gln	missense	Exon 2 of 2	NP_542432.2	Q9BQ50-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TREX2	ENST00000370231.3	TSL:5 MANE Select	c.446C>A	p.Pro149Gln	missense	Exon 2 of 2	ENSP00000359251.2	Q9BQ50-2
TREX2	ENST00000334497.7	TSL:1	c.575C>A	p.Pro192Gln	missense	Exon 11 of 11	ENSP00000334993.2	Q9BQ50-1
TREX2	ENST00000370232.4	TSL:1	c.575C>A	p.Pro192Gln	missense	Exon 11 of 11	ENSP00000359252.1	Q9BQ50-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000869

AC:

AN:

115100

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000488

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000188

AC:

AN:

1064681

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

344657

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25822

American (AMR)

AF:

0.0000336

AC:

AN:

29742

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18526

East Asian (EAS)

AF:

0.00

AC:

AN:

28735

South Asian (SAS)

AF:

0.00

AC:

AN:

50563

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37079

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3986

European-Non Finnish (NFE)

AF:

0.00000121

AC:

AN:

825466

Other (OTH)

AF:

0.00

AC:

AN:

44762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

4.6

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.096

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.50

M_CAP

Benign

0.020

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.74

PhyloP100

0.25

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.93

REVEL

Benign

0.11

Sift

Benign

0.49

Sift4G

Benign

0.61

Polyphen

0.69

Vest4

0.26

MutPred

0.36

Gain of helix (P = 0.0496)

MVP

0.17

MPC

0.023

ClinPred

0.20

GERP RS

5.0

Varity_R

0.14

gMVP

0.27

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over