14-22947180-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001166269.2(HAUS4):c.899G>A(p.Arg300His) variant causes a missense change. The variant allele was found at a frequency of 0.0000107 in 1,592,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

HAUS4
NM_001166269.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.15

Publications

1 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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36979145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAUS4	NM_001166269.2 link	c.899G>A	p.Arg300His	missense_variant	Exon 9 of 10	ENST00000541587.6	NP_001159741.1	Q9H6D7-1
HAUS4	NM_017815.3 link	c.899G>A	p.Arg300His	missense_variant	Exon 9 of 10		NP_060285.2	Q9H6D7-1
HAUS4	NM_001166270.2 link	c.764G>A	p.Arg255His	missense_variant	Exon 8 of 9		NP_001159742.1	Q9H6D7-4
PRMT5-DT	NR_110002.1 link	n.195-7151C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAUS4	ENST00000541587.6 link	c.899G>A	p.Arg300His	missense_variant	Exon 9 of 10	1	NM_001166269.2	ENSP00000441026.1		Q9H6D7-1
ENSG00000259132	ENST00000555074.1 link	c.386G>A	p.Arg129His	missense_variant	Exon 4 of 5	2		ENSP00000450856.2		G3V2T6

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151618

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

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:

0.0000239

AC:

AN:

251396

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

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:

0.000163

GnomAD4 exome

AF:

0.00000902

AC:

AN:

1440644

Hom.:

Cov.:

AF XY:

0.00000696

AC XY:

AN XY:

718258

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33068

American (AMR)

AF:

0.0000895

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26004

East Asian (EAS)

AF:

0.00

AC:

AN:

39598

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85840

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.00000458

AC:

AN:

1092732

Other (OTH)

AF:

0.0000336

AC:

AN:

59574

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151618

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74010

show subpopulations

African (AFR)

AF:

0.0000484

AC:

AN:

41354

American (AMR)

AF:

0.000132

AC:

AN:

15182

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10512

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67864

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 12, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.899G>A (p.R300H) alteration is located in exon 9 (coding exon 8) of the HAUS4 gene. This alteration results from a G to A substitution at nucleotide position 899, causing the arginine (R) at amino acid position 300 to be replaced by a histidine (H). 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

0.082

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.042

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

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.78

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

M_CAP

Benign

0.017

MetaRNN

Benign

0.37

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

MetaSVM

Benign

-0.29

MutationAssessor

Uncertain

2.4

.;M;M;.;.;.;.

PhyloP100

4.1

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.96

N;N;N;N;N;N;N

REVEL

Uncertain

0.34

Sift

Uncertain

0.0040

D;D;D;D;D;D;D

Sift4G

Uncertain

0.0080

D;D;D;D;D;D;D

Polyphen

1.0, 1.0

.;D;D;D;D;D;D

Vest4

0.38

MutPred

0.42

.;Gain of catalytic residue at K295 (P = 0.0157);Gain of catalytic residue at K295 (P = 0.0157);.;.;.;.;

MVP

0.75

MPC

0.27

ClinPred

0.35

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.25

Mutation Taster

=84/16

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.

14-22947180-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over