Genetic Variant HAUS3:p.Thr440Ile (chr4-2238634-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001303143.2(HAUS3):c.1319C>T(p.Thr440Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HAUS3
NM_001303143.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.45

Variant links:

Genes affected

HAUS3 (HGNC:28719): (HAUS augmin like complex subunit 3) This gene encodes a component of the HAUS augmin-like protein complex, which plays a key role in cytokinesis and mitosis. Disruption of the encoded protein causes mitotic defects resulting from fragmentation of centrosomes and microtubule destabilization. This gene shares its 5' exons with some transcripts from overlapping GeneID: 353497, which encodes a DNA polymerase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

HAUS3 links:

POLN (HGNC:18870): (DNA polymerase nu) This gene encodes a DNA polymerase type-A family member. The encoded protein plays a role in DNA repair and homologous recombination. This gene shares its 5' exons with some transcripts from overlapping GeneID: 79441, which encodes an augmentin-like protein complex subunit. [provided by RefSeq, Dec 2014]

POLN links:

ENSG00000290263 (HGNC:):

ENSG00000290263 links:

COX6B1P5 (HGNC:37675): (cytochrome c oxidase subunit 6B1 pseudogene 5)

COX6B1P5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15703085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAUS3	NM_001303143.2 link	c.1319C>T	p.Thr440Ile	missense_variant	Exon 4 of 6	ENST00000443786.3	NP_001290072.1	Q68CZ6-1
POLN	NM_181808.4 link	c.-13+2886C>T		intron_variant	Intron 2 of 25	ENST00000511885.6	NP_861524.2	Q7Z5Q5-1
HAUS3	NM_024511.7 link	c.1319C>T	p.Thr440Ile	missense_variant	Exon 3 of 5		NP_078787.2	Q68CZ6-1
COX6B1P5		n.2238634G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HAUS3	ENST00000443786.3 link	c.1319C>T	p.Thr440Ile	missense_variant	Exon 4 of 6	1	NM_001303143.2	ENSP00000392903.2	Q68CZ6-1
POLN	ENST00000511885.6 link	c.-13+2886C>T		intron_variant	Intron 2 of 25	5	NM_181808.4	ENSP00000435506.1	Q7Z5Q5-1
ENSG00000290263	ENST00000672725.1 link	n.1319C>T		non_coding_transcript_exon_variant	Exon 3 of 19			ENSP00000500518.1	A0A5F9ZHQ7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1454146

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723612

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.43

.;T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

0.042

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.66

T;.;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;M;M

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Benign

0.040

Sift

Uncertain

0.019

D;D;D

Sift4G

Uncertain

0.021

D;D;D

Polyphen

0.024

.;B;B

Vest4

0.29

MutPred

0.23

Loss of glycosylation at T440 (P = 0.0328);Loss of glycosylation at T440 (P = 0.0328);Loss of glycosylation at T440 (P = 0.0328);

MVP

0.45

MPC

0.020

ClinPred

0.61

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.16

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over