dbSNP rs1173814112: TREX2:p.Thr142Thr (chrX-153445005-A-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_080701.4(TREX2):c.426T>C(p.Thr142Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000341 in 1,174,062 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.0000028 ( 0 hom. 0 hem. )

Consequence

TREX2
NM_080701.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.709

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant X-153445005-A-G is Benign according to our data. Variant chrX-153445005-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2661689.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.709 with no splicing effect.

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.426T>C	p.Thr142Thr	synonymous	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.426T>C	p.Thr142Thr	synonymous	Exon 2 of 2	ENSP00000359251.2	Q9BQ50-2
TREX2	ENST00000334497.7	TSL:1	c.555T>C	p.Thr185Thr	synonymous	Exon 11 of 11	ENSP00000334993.2	Q9BQ50-1
TREX2	ENST00000370232.4	TSL:1	c.555T>C	p.Thr185Thr	synonymous	Exon 11 of 11	ENSP00000359252.1	Q9BQ50-1

Frequencies

GnomAD3 genomes

AF:

0.00000887

AC:

AN:

112800

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000322

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000266

AC:

AN:

112643

AF XY:

0.0000297

show subpopulations

Gnomad AFR exome

AF:

0.000153

Gnomad AMR exome

AF:

0.0000496

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:

0.000323

GnomAD4 exome

AF:

0.00000283

AC:

AN:

1061262

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

342536

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25676

American (AMR)

AF:

0.0000341

AC:

AN:

29317

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18357

East Asian (EAS)

AF:

0.0000350

AC:

AN:

28557

South Asian (SAS)

AF:

0.00

AC:

AN:

49987

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37008

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4006

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

823769

Other (OTH)

AF:

0.0000224

AC:

AN:

44585

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

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

AF:

0.00000887

AC:

AN:

112800

Hom.:

Cov.:

AF XY:

0.0000286

AC XY:

AN XY:

35010

show subpopulations

African (AFR)

AF:

0.0000322

AC:

AN:

31094

American (AMR)

AF:

0.00

AC:

AN:

10831

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3518

South Asian (SAS)

AF:

0.00

AC:

AN:

2833

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6279

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53150

Other (OTH)

AF:

0.00

AC:

AN:

1531

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.82

(source)

DANN

Benign

0.63

PhyloP100

-0.71

Mutation Taster

=100/0

polymorphism

(source)

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

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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