Genetic Variant NM_001166269.2:c.613G>A (chr14-22947963-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001166269.2(HAUS4):c.613G>A(p.Val205Ile) 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 152,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V205F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Consequence

HAUS4
NM_001166269.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.192

Publications

0 publications found

Variant links:

Genes affected

HAUS4 (HGNC:20163): (HAUS augmin like complex subunit 4) This gene encodes a subunit of the centrosome complex termed the human augmin complex. The encoded protein localizes to the spindle microtubules and may play a role in mitotic spindle assembly and maintenance of centrosome integrity during cell division. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 1. [provided by RefSeq, Oct 2009]

HAUS4 links:

ENSG00000259132 (HGNC:):

ENSG00000259132 links:

PRMT5-DT (HGNC:55482): (PRMT5 divergent transcript)

PRMT5-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.101145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAUS4	NM_001166269.2 link	c.613G>A	p.Val205Ile	missense_variant	Exon 7 of 10	ENST00000541587.6	NP_001159741.1	Q9H6D7-1
HAUS4	NM_017815.3 link	c.613G>A	p.Val205Ile	missense_variant	Exon 7 of 10		NP_060285.2	Q9H6D7-1
HAUS4	NM_001166270.2 link	c.478G>A	p.Val160Ile	missense_variant	Exon 6 of 9		NP_001159742.1	Q9H6D7-4
PRMT5-DT	NR_110002.1 link	n.195-6368C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAUS4	ENST00000541587.6 link	c.613G>A	p.Val205Ile	missense_variant	Exon 7 of 10	1	NM_001166269.2	ENSP00000441026.1		Q9H6D7-1
ENSG00000259132	ENST00000555074.1 link	c.100G>A	p.Val34Ile	missense_variant	Exon 2 of 5	2		ENSP00000450856.2		G3V2T6

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152136

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

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41432

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.020

.;T;T;.;.;.;T

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.72

T;.;T;.;.;T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.10

T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.97

.;L;L;.;.;.;.

PhyloP100

0.19

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.16

N;N;N;N;N;N;N

REVEL

Benign

0.026

Sift

Benign

0.46

T;T;T;T;T;T;T

Sift4G

Benign

0.60

T;T;T;T;T;T;.

Polyphen

0.0010, 0.0

.;B;B;B;B;B;.

Vest4

0.12

MutPred

0.34

.;Gain of catalytic residue at V207 (P = 0.0034);Gain of catalytic residue at V207 (P = 0.0034);.;.;.;Gain of catalytic residue at V207 (P = 0.0034);

MVP

0.32

MPC

0.17

ClinPred

0.11

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.018

gMVP

0.053

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over