Variant 18-46128093-C-G 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_138443.4(HAUS1):c.805C>G(p.Leu269Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,586,664 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

HAUS1
NM_138443.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.58

Variant links:

Genes affected

HAUS1 (HGNC:25174): (HAUS augmin like complex subunit 1) HAUS1 is 1 of 8 subunits of the 390-kD human augmin complex, or HAUS complex. The augmin complex was first identified in Drosophila, and its name comes from the Latin verb 'augmentare,' meaning 'to increase.' The augmin complex is a microtubule-binding complex involved in microtubule generation within the mitotic spindle and is vital to mitotic spindle assembly (Goshima et al., 2008 [PubMed 18443220]; Uehara et al., 2009 [PubMed 19369198]).[supplied by OMIM, Jun 2010]

HAUS1 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=0.009005457).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAUS1	NM_138443.4 linkuse as main transcript	c.805C>G	p.Leu269Val	missense_variant	9/9	ENST00000282058.11
HAUS1	NR_026978.2 linkuse as main transcript	n.872C>G		non_coding_transcript_exon_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAUS1	ENST00000282058.11 linkuse as main transcript	c.805C>G	p.Leu269Val	missense_variant	9/9	1	NM_138443.4	P1	Q96CS2-1

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000438

AC:

102

AN:

232892

Hom.:

AF XY:

0.000475

AC XY:

AN XY:

126412

show subpopulations

Gnomad AFR exome

AF:

0.000127

Gnomad AMR exome

AF:

0.0000354

Gnomad ASJ exome

AF:

0.00778

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000211

Gnomad OTH exome

AF:

0.000356

GnomAD4 exome

AF:

0.000233

AC:

334

AN:

1434570

Hom.:

Cov.:

AF XY:

0.000252

AC XY:

180

AN XY:

713972

show subpopulations

Gnomad4 AFR exome

AF:

0.0000619

Gnomad4 AMR exome

AF:

0.0000520

Gnomad4 ASJ exome

AF:

0.00754

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000926

Gnomad4 OTH exome

AF:

0.000610

GnomAD4 genome

AF:

0.000263

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000663

Hom.:

Bravo

AF:

0.000283

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000272

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 01, 2021

The c.805C>G (p.L269V) alteration is located in exon 9 (coding exon 9) of the HAUS1 gene. This alteration results from a C to G substitution at nucleotide position 805, causing the leucine (L) at amino acid position 269 to be replaced by a valine (V). 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

0.15

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.16

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.046

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.76

M_CAP

Benign

0.0090

MetaRNN

Benign

0.0090

MetaSVM

Uncertain

-0.19

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.6

REVEL

Benign

0.23

Sift

Uncertain

0.013

Sift4G

Uncertain

0.017

Polyphen

0.99

Vest4

0.31

MVP

0.53

MPC

0.34

ClinPred

0.13

GERP RS

5.1

Varity_R

0.23

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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