14-22948007-T-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001166269.2(HAUS4):c.569A>C(p.Asp190Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000466 in 1,609,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

HAUS4
NM_001166269.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.60

Publications

0 publications found

Variant links:

Genes affected

HAUS4 (HGNC:20163): (HAUS augmin like complex subunit 4) This gene encodes a subunit of the centrosome complex termed the human augmin complex. The encoded protein localizes to the spindle microtubules and may play a role in mitotic spindle assembly and maintenance of centrosome integrity during cell division. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 1. [provided by RefSeq, Oct 2009]

HAUS4 links:

ENSG00000259132 (HGNC:):

ENSG00000259132 links:

PRMT5-DT (HGNC:55482): (PRMT5 divergent transcript)

PRMT5-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05824116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAUS4	NM_001166269.2 link	c.569A>C	p.Asp190Ala	missense_variant	Exon 7 of 10	ENST00000541587.6	NP_001159741.1	Q9H6D7-1
HAUS4	NM_017815.3 link	c.569A>C	p.Asp190Ala	missense_variant	Exon 7 of 10		NP_060285.2	Q9H6D7-1
HAUS4	NM_001166270.2 link	c.434A>C	p.Asp145Ala	missense_variant	Exon 6 of 9		NP_001159742.1	Q9H6D7-4
PRMT5-DT	NR_110002.1 link	n.195-6324T>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAUS4	ENST00000541587.6 link	c.569A>C	p.Asp190Ala	missense_variant	Exon 7 of 10	1	NM_001166269.2	ENSP00000441026.1		Q9H6D7-1
ENSG00000259132	ENST00000555074.1 link	c.56A>C	p.Asp19Ala	missense_variant	Exon 2 of 5	2		ENSP00000450856.2		G3V2T6

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000702

AC:

AN:

242252

AF XY:

0.0000457

show subpopulations

Gnomad AFR exome

AF:

0.000442

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000334

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000302

AC:

AN:

1457230

Hom.:

Cov.:

AF XY:

0.0000235

AC XY:

AN XY:

724852

show subpopulations

African (AFR)

AF:

0.000390

AC:

AN:

33312

American (AMR)

AF:

0.00

AC:

AN:

43576

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25852

East Asian (EAS)

AF:

0.000151

AC:

AN:

39660

South Asian (SAS)

AF:

0.0000934

AC:

AN:

85616

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53184

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1110066

Other (OTH)

AF:

0.000266

AC:

AN:

60220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000204

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.000555

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000385

AC:

AN:

5200

South Asian (SAS)

AF:

0.00124

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000918

Hom.:

Bravo

AF:

0.000238

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 08, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.569A>C (p.D190A) alteration is located in exon 7 (coding exon 6) of the HAUS4 gene. This alteration results from a A to C substitution at nucleotide position 569, causing the aspartic acid (D) at amino acid position 190 to be replaced by an alanine (A). 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

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

.;T;T;.;.;.;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.078

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.75

T;.;T;.;.;T;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.058

T;T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.8

.;L;L;.;.;.;.

PhyloP100

2.6

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.0

N;N;N;N;N;N;D

REVEL

Benign

0.11

Sift

Benign

0.17

T;T;T;T;T;T;T

Sift4G

Benign

0.36

T;T;T;D;D;D;.

Polyphen

0.13, 0.026

.;B;B;B;B;B;.

Vest4

0.25

MVP

0.68

MPC

0.80

ClinPred

0.033

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.18

Mutation Taster

=88/12

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

14-22948007-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over