NM_001303143.2:c.1757T>C

Variant names:

• chr4-2231982-A-G
• rs11937432
• NM_001303143.2:c.1757T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001303143.2(HAUS3):​c.1757T>C​(p.Ile586Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0498 in 1,487,268 control chromosomes in the GnomAD database, including 2,493 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.081 (736 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1757 hom.)
• Consequence: HAUS3 NM_001303143.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.58
• Publications: 26 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:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012872815).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAUS3	NM_001303143.2	MANE Select	c.1757T>C	p.Ile586Thr	missense	Exon 6 of 6	NP_001290072.1
	POLN	NM_181808.4	MANE Select	c.-12-2739T>C		intron	N/A	NP_861524.2
	HAUS3	NM_024511.7		c.1757T>C	p.Ile586Thr	missense	Exon 5 of 5	NP_078787.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAUS3	ENST00000443786.3	TSL:1 MANE Select	c.1757T>C	p.Ile586Thr	missense	Exon 6 of 6	ENSP00000392903.2
	HAUS3	ENST00000243706.8	TSL:1	c.1757T>C	p.Ile586Thr	missense	Exon 5 of 5	ENSP00000243706.4
	POLN	ENST00000511885.6	TSL:5 MANE Select	c.-12-2739T>C		intron	N/A	ENSP00000435506.1

Frequencies

GnomAD3 genomes AF: 0.0805 AC: 12249 AN: 152078 Hom.: 733 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0666

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.0291

Gnomad SAS AF: 0.0415

Gnomad FIN AF: 0.0539

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0487

Gnomad OTH AF: 0.0631

GnomAD2 exomes AF: 0.0590 AC: 13806 AN: 234040 AF XY: 0.0555

Gnomad AFR exome AF: 0.153

Gnomad AMR exome AF: 0.0776

Gnomad ASJ exome AF: 0.0610

Gnomad EAS exome AF: 0.0325

Gnomad FIN exome AF: 0.0612

Gnomad NFE exome AF: 0.0483

Gnomad OTH exome AF: 0.0649

GnomAD4 exome AF: 0.0463 AC: 61831 AN: 1335072 Hom.: 1757 Cov.: 22 AF XY: 0.0463 AC XY: 30996 AN XY: 669478

African (AFR) AF: 0.152 AC: 4578 AN: 30096

American (AMR) AF: 0.0750 AC: 3096 AN: 41270

Ashkenazi Jewish (ASJ) AF: 0.0576 AC: 1443 AN: 25070

East Asian (EAS) AF: 0.0356 AC: 1375 AN: 38598

South Asian (SAS) AF: 0.0419 AC: 3339 AN: 79746

European-Finnish (FIN) AF: 0.0580 AC: 3077 AN: 53012

Middle Eastern (MID) AF: 0.0956 AC: 527 AN: 5514

European-Non Finnish (NFE) AF: 0.0412 AC: 41428 AN: 1005854

Other (OTH) AF: 0.0531 AC: 2968 AN: 55912

GnomAD4 genome AF: 0.0806 AC: 12270 AN: 152196 Hom.: 736 Cov.: 32 AF XY: 0.0790 AC XY: 5878 AN XY: 74428

African (AFR) AF: 0.157 AC: 6533 AN: 41510

American (AMR) AF: 0.0664 AC: 1016 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3468

East Asian (EAS) AF: 0.0289 AC: 150 AN: 5182

South Asian (SAS) AF: 0.0421 AC: 203 AN: 4820

European-Finnish (FIN) AF: 0.0539 AC: 571 AN: 10596

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0487 AC: 3310 AN: 68010

Other (OTH) AF: 0.0624 AC: 132 AN: 2114

Alfa AF: 0.0584 Hom.: 1529

Bravo AF: 0.0841

TwinsUK AF: 0.0413 AC: 153

ALSPAC AF: 0.0441 AC: 170

ESP6500AA AF: 0.142 AC: 620

ESP6500EA AF: 0.0513 AC: 435

ExAC AF: 0.0595 AC: 7214

Asia WGS AF: 0.0450 AC: 156 AN: 3430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.012
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.62	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.6
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.055
Sift	Benign	0.037	D
Sift4G	Uncertain	0.013	D
Polyphen		0.017	B
Vest4		0.046
MPC		0.020
ClinPred		0.016	T
GERP RS		4.9
Varity_R		0.054
gMVP		0.090
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11937432; hg19: chr4-2233709; COSMIC: COSV104543815; COSMIC: COSV104543815;