Variant X-153455628-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001385482.1(HAUS7):c.844G>A(p.Glu282Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,207,880 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 52 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.00013 ( 0 hom. 51 hem. )

Consequence

HAUS7
NM_001385482.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.341

Variant links:

Genes affected

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:

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.097096086).

BS2

High Hemizygotes in GnomAdExome4 at 51 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAUS7	NM_001385482.1 link	c.844G>A	p.Glu282Lys	missense_variant	Exon 8 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.844G>A	p.Glu282Lys	missense_variant	Exon 8 of 10	1	NM_001385482.1	ENSP00000359230.6		Q99871-1

Frequencies

GnomAD3 genomes

AF:

0.0000266

AC:

AN:

112586

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

34746

show subpopulations

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:

0.000364

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000382

AC:

AN:

183378

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

67856

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000366

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000127

AC:

139

AN:

1095294

Hom.:

Cov.:

AF XY:

0.000141

AC XY:

AN XY:

360750

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000160

Gnomad4 OTH exome

AF:

0.0000652

GnomAD4 genome

AF:

0.0000266

AC:

AN:

112586

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

34746

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000364

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 24, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.874G>A (p.E292K) alteration is located in exon 8 (coding exon 8) of the HAUS7 gene. This alteration results from a G to A substitution at nucleotide position 874, causing the glutamic acid (E) at amino acid position 292 to be replaced by a lysine (K). 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

0.092

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.062

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.74

M_CAP

Benign

0.015

MetaRNN

Benign

0.097

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.37

REVEL

Benign

0.13

Sift4G

Uncertain

0.018

Polyphen

0.51

Vest4

0.24

MVP

0.63

MPC

0.29

ClinPred

0.074

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.24

gMVP

0.20

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

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