Variant chr4-2236312-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001303143.2(HAUS3):c.1494C>A(p.Phe498Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

HAUS3
NM_001303143.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.229

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018284708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HAUS3	NM_001303143.2 linkuse as main transcript	c.1494C>A	p.Phe498Leu	missense_variant	5/6	ENST00000443786.3
POLN	NM_181808.4 linkuse as main transcript	c.-13+5208C>A		intron_variant		ENST00000511885.6
HAUS3	NM_024511.7 linkuse as main transcript	c.1494C>A	p.Phe498Leu	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAUS3	ENST00000443786.3 linkuse as main transcript	c.1494C>A	p.Phe498Leu	missense_variant	5/6	1	NM_001303143.2	P1	Q68CZ6-1
POLN	ENST00000511885.6 linkuse as main transcript	c.-13+5208C>A		intron_variant		5	NM_181808.4	P1	Q7Z5Q5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251326

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000435

Gnomad SAS 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:

0.00000547

AC:

AN:

1461446

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727042

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2023

The c.1494C>A (p.F498L) alteration is located in exon 4 (coding exon 3) of the HAUS3 gene. This alteration results from a C to A substitution at nucleotide position 1494, causing the phenylalanine (F) at amino acid position 498 to be replaced by a leucine (L). 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

0.24

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.63

CADD

Benign

5.4

DANN

Benign

0.90

DEOGEN2

Benign

0.042

T;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.22

M_CAP

Benign

0.0036

MetaRNN

Benign

0.018

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.40

N;N

MutationTaster

Benign

1.0

D;N;N;D

PrimateAI

Benign

0.33

PROVEAN

Benign

0.040

N;N

REVEL

Benign

0.12

Sift

Benign

0.70

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.13

MutPred

0.27

Loss of ubiquitination at K502 (P = 0.1151);Loss of ubiquitination at K502 (P = 0.1151);

MVP

0.10

MPC

0.019

ClinPred

0.063

GERP RS

-0.55

Varity_R

0.017

gMVP

0.14

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over