14-22947211-T-C

Variant summary

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

The NM_001166269.2(HAUS4):​c.868A>G​(p.Thr290Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T290S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

HAUS4
NM_001166269.2 missense

Scores

1
7
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.03

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)

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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=0.29795858).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HAUS4NM_001166269.2 linkc.868A>G p.Thr290Ala missense_variant Exon 9 of 10 ENST00000541587.6 NP_001159741.1 Q9H6D7-1
HAUS4NM_017815.3 linkc.868A>G p.Thr290Ala missense_variant Exon 9 of 10 NP_060285.2 Q9H6D7-1
HAUS4NM_001166270.2 linkc.733A>G p.Thr245Ala missense_variant Exon 8 of 9 NP_001159742.1 Q9H6D7-4
PRMT5-DTNR_110002.1 linkn.195-7120T>C intron_variant Intron 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HAUS4ENST00000541587.6 linkc.868A>G p.Thr290Ala missense_variant Exon 9 of 10 1 NM_001166269.2 ENSP00000441026.1 Q9H6D7-1
ENSG00000259132ENST00000555074.1 linkc.355A>G p.Thr119Ala missense_variant Exon 4 of 5 2 ENSP00000450856.2 G3V2T6

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251400
AF XY:
0.00000736
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:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1457764
Hom.:
0
Cov.:
28
AF XY:
0.00000138
AC XY:
1
AN XY:
725536
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33424
American (AMR)
AF:
0.00
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26114
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39672
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86138
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53382
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
9.02e-7
AC:
1
AN:
1108320
Other (OTH)
AF:
0.00
AC:
0
AN:
60232
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
31
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.10
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.35
.;T;T;.;.;.;.
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.66
T;.;T;.;T;.;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.30
T;T;T;T;T;T;T
MetaSVM
Benign
-0.55
T
MutationAssessor
Uncertain
2.1
.;M;M;.;.;.;.
PhyloP100
2.0
PrimateAI
Benign
0.45
T
PROVEAN
Uncertain
-3.3
D;D;D;D;D;D;D
REVEL
Benign
0.27
Sift
Benign
0.064
T;T;T;T;D;T;T
Sift4G
Benign
0.35
T;T;T;T;T;T;T
Polyphen
1.0, 0.97
.;D;D;D;D;D;D
Vest4
0.41
MutPred
0.53
.;Gain of catalytic residue at K295 (P = 0.039);Gain of catalytic residue at K295 (P = 0.039);.;.;.;.;
MVP
0.74
MPC
0.21
ClinPred
0.74
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.23
gMVP
0.61
Mutation Taster
=70/30
polymorphism

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

Other links and lift over

dbSNP: rs763188023; hg19: chr14-23416420; API