Variant X-153454438-C-A 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.1001G>T(p.Gly334Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,153,413 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 77 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 0.00010 ( 0 hom., 2 hem., cov: 21)

Exomes 𝑓: 0.00023 ( 0 hom. 75 hem. )

Consequence

HAUS7
NM_001385482.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.00

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=0.11019263).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAUS7	NM_001385482.1 link	c.1001G>T	p.Gly334Val	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.1001G>T	p.Gly334Val	missense_variant	Exon 9 of 10	1	NM_001385482.1	ENSP00000359230.6		Q99871-1

Frequencies

GnomAD3 genomes

AF:

0.000104

AC:

AN:

105953

Hom.:

Cov.:

AF XY:

0.0000678

AC XY:

AN XY:

29509

show subpopulations

Gnomad AFR

AF:

0.0000343

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:

0.000194

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000549

AC:

AN:

182100

Hom.:

AF XY:

0.0000298

AC XY:

AN XY:

67016

show subpopulations

Gnomad AFR exome

AF:

0.0000765

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000111

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000230

AC:

241

AN:

1047460

Hom.:

Cov.:

AF XY:

0.000223

AC XY:

AN XY:

336810

show subpopulations

Gnomad4 AFR exome

AF:

0.0000799

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000278

Gnomad4 OTH exome

AF:

0.000349

GnomAD4 genome

AF:

0.000104

AC:

AN:

105953

Hom.:

Cov.:

AF XY:

0.0000678

AC XY:

AN XY:

29509

show subpopulations

Gnomad4 AFR

AF:

0.0000343

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000194

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.000174

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1031G>T (p.G344V) alteration is located in exon 9 (coding exon 9) of the HAUS7 gene. This alteration results from a G to T substitution at nucleotide position 1031, causing the glycine (G) at amino acid position 344 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.59

CADD

Benign

2.8

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.60

M_CAP

Benign

0.017

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.22

REVEL

Benign

0.098

Sift4G

Uncertain

0.028

Polyphen

0.81

Vest4

0.33

MutPred

0.28

Loss of ubiquitination at K341 (P = 0.045);

MVP

0.46

MPC

0.55

ClinPred

0.22

GERP RS

-2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.13

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