14-22947180-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.15
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 made for transcript

Verdict is Uncertain_significance. Variant got 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
HAUS4NM_001166269.2 linkc.899G>A p.Arg300His missense_variant Exon 9 of 10 ENST00000541587.6 NP_001159741.1 Q9H6D7-1
HAUS4NM_017815.3 linkc.899G>A p.Arg300His missense_variant Exon 9 of 10 NP_060285.2 Q9H6D7-1
HAUS4NM_001166270.2 linkc.764G>A p.Arg255His missense_variant Exon 8 of 9 NP_001159742.1 Q9H6D7-4
PRMT5-DTNR_110002.1 linkn.195-7151C>T intron_variant Intron 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HAUS4ENST00000541587.6 linkc.899G>A p.Arg300His missense_variant Exon 9 of 10 1 NM_001166269.2 ENSP00000441026.1 Q9H6D7-1
ENSG00000259132ENST00000555074.1 linkc.386G>A p.Arg129His missense_variant Exon 4 of 5 2 ENSP00000450856.2 G3V2T6

Frequencies

GnomAD3 genomes
AF:
0.0000264
AC:
4
AN:
151618
Hom.:
0
Cov.:
31
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
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251396
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135894
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 SAS 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:
13
AN:
1440644
Hom.:
0
Cov.:
28
AF XY:
0.00000696
AC XY:
5
AN XY:
718258
show subpopulations
Gnomad4 AFR exome
AF:
0.0000302
Gnomad4 AMR exome
AF:
0.0000895
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000458
Gnomad4 OTH exome
AF:
0.0000336
GnomAD4 genome
AF:
0.0000264
AC:
4
AN:
151618
Hom.:
0
Cov.:
31
AF XY:
0.0000405
AC XY:
3
AN XY:
74010
show subpopulations
Gnomad4 AFR
AF:
0.0000484
Gnomad4 AMR
AF:
0.000132
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ExAC
AF:
0.0000165
AC:
2
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
T
BayesDel_noAF
Benign
-0.18
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.042
.;T;T;.;.;.;.
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.78
T;.;T;.;T;.;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.37
T;T;T;T;T;T;T
MetaSVM
Benign
-0.29
T
MutationAssessor
Uncertain
2.4
.;M;M;.;.;.;.
PrimateAI
Uncertain
0.60
T
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
T
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.18
gMVP
0.25

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs762041209; hg19: chr14-23416389; COSMIC: COSV104392203; COSMIC: COSV104392203; API