chr14-22947214-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001166269.2(HAUS4):​c.865G>A​(p.Asp289Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000185 in 1,456,866 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: not found (cov: 31)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

HAUS4
NM_001166269.2 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.47

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.28558886).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HAUS4NM_001166269.2 linkc.865G>A p.Asp289Asn missense_variant Exon 9 of 10 ENST00000541587.6 NP_001159741.1 Q9H6D7-1
HAUS4NM_017815.3 linkc.865G>A p.Asp289Asn missense_variant Exon 9 of 10 NP_060285.2 Q9H6D7-1
HAUS4NM_001166270.2 linkc.730G>A p.Asp244Asn missense_variant Exon 8 of 9 NP_001159742.1 Q9H6D7-4
PRMT5-DTNR_110002.1 linkn.195-7117C>T intron_variant Intron 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HAUS4ENST00000541587.6 linkc.865G>A p.Asp289Asn missense_variant Exon 9 of 10 1 NM_001166269.2 ENSP00000441026.1 Q9H6D7-1
ENSG00000259132ENST00000555074.1 linkc.352G>A p.Asp118Asn missense_variant Exon 4 of 5 2 ENSP00000450856.2 G3V2T6

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD2 exomes
AF:
0.0000438
AC:
11
AN:
251382
AF XY:
0.0000515
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00
GnomAD4 exome
AF:
0.0000185
AC:
27
AN:
1456866
Hom.:
0
Cov.:
28
AF XY:
0.0000290
AC XY:
21
AN XY:
725108
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33406
American (AMR)
AF:
0.00
AC:
0
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26108
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39670
South Asian (SAS)
AF:
0.000267
AC:
23
AN:
86090
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53388
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
9.03e-7
AC:
1
AN:
1107502
Other (OTH)
AF:
0.0000332
AC:
2
AN:
60224
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.445
Heterozygous variant carriers
0
2
4
6
8
10
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.0000659
AC:
8
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 26, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.865G>A (p.D289N) 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 865, causing the aspartic acid (D) at amino acid position 289 to be replaced by an asparagine (N). 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
0.15
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.35
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.23
.;T;T;.;.;.;.
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.80
T;.;T;.;T;.;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.29
T;T;T;T;T;T;T
MetaSVM
Benign
-0.34
T
MutationAssessor
Uncertain
2.4
.;M;M;.;.;.;.
PhyloP100
4.5
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-3.1
D;D;D;D;D;D;D
REVEL
Benign
0.16
Sift
Benign
0.036
D;T;T;T;D;T;T
Sift4G
Uncertain
0.030
D;D;D;D;D;D;D
Polyphen
1.0, 1.0
.;D;D;D;D;D;D
Vest4
0.50
MutPred
0.39
.;Gain of relative solvent accessibility (P = 0.0275);Gain of relative solvent accessibility (P = 0.0275);.;.;.;.;
MVP
0.75
MPC
0.75
ClinPred
0.76
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.32
gMVP
0.40
Mutation Taster
=86/14
polymorphism

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

Other links and lift over

dbSNP: rs771325556; hg19: chr14-23416423; API