Variant X-153454463-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000334497.7(TREX2):c.-137G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000684 in 1,131,382 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 238 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00078 ( 0 hom., 20 hem., cov: 20)

Exomes 𝑓: 0.00067 ( 0 hom. 218 hem. )

Consequence

TREX2
ENST00000334497.7 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.26

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:

HAUS7 (HGNC:32979): (HAUS augmin like complex subunit 7) This gene encodes a subunit of the augmin complex, which regulates centrosome and mitotic spindle integrity, and is necessary for the completion of cytokinesis. The encoded protein was identified by interaction with ubiquitin C-terminal hydrolase 37. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012]

HAUS7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048015714).

BS2

High Hemizygotes in GnomAd4 at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAUS7	NM_001385482.1 link	c.976G>A	p.Val326Met	missense_variant	Exon 9 of 10	ENST00000370211.10	NP_001372411.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAUS7	ENST00000370211.10 link	c.976G>A	p.Val326Met	missense_variant	Exon 9 of 10	1	NM_001385482.1	ENSP00000359230.6		Q99871-1

Frequencies

GnomAD3 genomes

AF:

0.000782

AC:

AN:

99748

Hom.:

Cov.:

AF XY:

0.000793

AC XY:

AN XY:

25224

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000446

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:

0.000422

Gnomad OTH

AF:

0.00152

GnomAD3 exomes

AF:

0.000344

AC:

AN:

179972

Hom.:

AF XY:

0.000320

AC XY:

AN XY:

65524

show subpopulations

Gnomad AFR exome

AF:

0.00224

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000535

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000402

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000675

AC:

696

AN:

1031606

Hom.:

Cov.:

AF XY:

0.000663

AC XY:

218

AN XY:

328832

show subpopulations

Gnomad4 AFR exome

AF:

0.00244

Gnomad4 AMR exome

AF:

0.0000294

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000561

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000770

Gnomad4 OTH exome

AF:

0.000523

GnomAD4 genome

AF:

0.000782

AC:

AN:

99776

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

25256

show subpopulations

Gnomad4 AFR

AF:

0.00190

Gnomad4 AMR

AF:

0.000446

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000422

Gnomad4 OTH

AF:

0.00150

Alfa

AF:

0.000336

Hom.:

Bravo

AF:

0.000790

ESP6500AA

AF:

0.00183

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000338

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1006G>A (p.V336M) alteration is located in exon 9 (coding exon 9) of the HAUS7 gene. This alteration results from a G to A substitution at nucleotide position 1006, causing the valine (V) at amino acid position 336 to be replaced by a methionine (M). 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

0.074

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.0090

DANN

Benign

0.77

DEOGEN2

Benign

0.018

FATHMM_MKL

Benign

0.0055

LIST_S2

Benign

0.47

M_CAP

Benign

0.0034

MetaRNN

Benign

0.0048

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.58

PrimateAI

Benign

0.25

REVEL

Benign

0.0080

Sift4G

Benign

0.23

Polyphen

0.22

Vest4

0.11

MVP

0.22

MPC

0.22

ClinPred

0.0033

GERP RS

-3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.029

gMVP

0.15

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over