4-2238745-C-A

Variant names:

• chr4-2238745-C-A
• rs765975164
• NM_001303143.2:c.1208G>T
• HAUS3 p.Arg403Leu

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001303143.2(HAUS3):​c.1208G>T​(p.Arg403Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HAUS3 NM_001303143.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.75
• Publications: 0 publications found

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]

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]

ENSG00000290263 (HGNC:):

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAUS3	NM_001303143.2	MANE Select	c.1208G>T	p.Arg403Leu	missense	Exon 4 of 6	NP_001290072.1	Q68CZ6-1
	POLN	NM_181808.4	MANE Select	c.-13+2775G>T		intron	N/A	NP_861524.2	Q7Z5Q5-1
	HAUS3	NM_024511.7		c.1208G>T	p.Arg403Leu	missense	Exon 3 of 5	NP_078787.2	Q68CZ6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAUS3	ENST00000443786.3	TSL:1 MANE Select	c.1208G>T	p.Arg403Leu	missense	Exon 4 of 6	ENSP00000392903.2	Q68CZ6-1
	HAUS3	ENST00000243706.8	TSL:1	c.1208G>T	p.Arg403Leu	missense	Exon 3 of 5	ENSP00000243706.4	Q68CZ6-1
	POLN	ENST00000511885.6	TSL:5 MANE Select	c.-13+2775G>T		intron	N/A	ENSP00000435506.1	Q7Z5Q5-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.8
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.19
Sift	Benign	0.11	T
Sift4G	Benign	0.18	T
Varity_R		0.099
gMVP		0.27
Mutation Taster		=73/27	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs765975164; hg19: chr4-2240472;