14-22950328-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001166269.2(HAUS4):c.548A>G(p.Tyr183Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00188 in 1,603,640 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0097 ( 18 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 33 hom. )

Consequence

HAUS4
NM_001166269.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.24

Publications

3 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061341524).

BP6

Variant 14-22950328-T-C is Benign according to our data. Variant chr14-22950328-T-C is described in ClinVar as [Benign]. Clinvar id is 719752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00968 (1473/152242) while in subpopulation AFR AF = 0.0334 (1389/41538). AF 95% confidence interval is 0.032. There are 18 homozygotes in GnomAd4. There are 724 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAUS4	NM_001166269.2 link	c.548A>G	p.Tyr183Cys	missense_variant	Exon 6 of 10	ENST00000541587.6	NP_001159741.1	Q9H6D7-1
HAUS4	NM_017815.3 link	c.548A>G	p.Tyr183Cys	missense_variant	Exon 6 of 10		NP_060285.2	Q9H6D7-1
HAUS4	NM_001166270.2 link	c.413A>G	p.Tyr138Cys	missense_variant	Exon 5 of 9		NP_001159742.1	Q9H6D7-4
PRMT5-DT	NR_110002.1 link	n.195-4003T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAUS4	ENST00000541587.6 link	c.548A>G	p.Tyr183Cys	missense_variant	Exon 6 of 10	1	NM_001166269.2	ENSP00000441026.1		Q9H6D7-1
ENSG00000259132	ENST00000555074.1 link	c.50-2315A>G		intron_variant	Intron 1 of 4	2		ENSP00000450856.2		G3V2T6

Frequencies

GnomAD3 genomes

AF:

0.00966

AC:

1470

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0335

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.0100

GnomAD2 exomes

AF:

0.00241

AC:

605

AN:

251430

AF XY:

0.00180

show subpopulations

Gnomad AFR exome

AF:

0.0329

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00106

AC:

1536

AN:

1451398

Hom.:

Cov.:

AF XY:

0.000914

AC XY:

661

AN XY:

722876

show subpopulations

African (AFR)

AF:

0.0382

AC:

1271

AN:

33232

American (AMR)

AF:

0.00148

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26068

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.0000697

AC:

AN:

86048

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0000336

AC:

AN:

1102518

Other (OTH)

AF:

0.00240

AC:

144

AN:

60006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

144

215

287

359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00968

AC:

1473

AN:

152242

Hom.:

Cov.:

AF XY:

0.00972

AC XY:

724

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0334

AC:

1389

AN:

41538

American (AMR)

AF:

0.00373

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68010

Other (OTH)

AF:

0.00994

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

141

211

282

352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00385

Hom.:

Bravo

AF:

0.0113

ESP6500AA

AF:

0.0309

AC:

136

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00315

AC:

383

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 24, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

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

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.66

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

MetaRNN

Benign

0.0061

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

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

PhyloP100

2.2

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-4.8

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

REVEL

Uncertain

0.45

Sift

Benign

0.037

D;D;D;D;D;D;D;T;D

Sift4G

Uncertain

0.016

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

Polyphen

0.0010, 0.92

.;B;B;P;P;P;.;.;.

Vest4

0.23

MVP

0.55

MPC

0.26

ClinPred

0.075

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.34

Mutation Taster

=96/4

polymorphism

(source)

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

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14-22950328-T-C

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