Genetic Variant NM_001303143.2:c.1414G>C (chr4-2236392-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_001303143.2(HAUS3):c.1414G>C(p.Glu472Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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)

Consequence

HAUS3
NM_001303143.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.63

Publications

0 publications found

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:

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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=0.29399908).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303143.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HAUS3	NM_001303143.2	MANE Select	c.1414G>C	p.Glu472Gln	missense	Exon 5 of 6	NP_001290072.1	Q68CZ6-1
POLN	NM_181808.4	MANE Select	c.-13+5128G>C		intron	N/A	NP_861524.2	Q7Z5Q5-1
HAUS3	NM_024511.7		c.1414G>C	p.Glu472Gln	missense	Exon 4 of 5	NP_078787.2	Q68CZ6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HAUS3	ENST00000443786.3	TSL:1 MANE Select	c.1414G>C	p.Glu472Gln	missense	Exon 5 of 6	ENSP00000392903.2	Q68CZ6-1
HAUS3	ENST00000243706.8	TSL:1	c.1414G>C	p.Glu472Gln	missense	Exon 4 of 5	ENSP00000243706.4	Q68CZ6-1
POLN	ENST00000511885.6	TSL:5 MANE Select	c.-13+5128G>C		intron	N/A	ENSP00000435506.1	Q7Z5Q5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.72

M_CAP

Benign

0.025

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.7

PhyloP100

2.6

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.91

REVEL

Benign

0.15

Sift

Uncertain

0.015

Sift4G

Pathogenic

0.0

Polyphen

0.84

Vest4

0.37

MutPred

0.46

Gain of ubiquitination at K477 (P = 0.1204)

MVP

0.39

MPC

0.050

ClinPred

0.89

GERP RS

4.9

Varity_R

0.14

gMVP

0.20

Mutation Taster

=64/36

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over