Genetic Variant HAUS6:p.Val817Met (chr9-19058318-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017645.5(HAUS6):c.2449G>A(p.Val817Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

HAUS6
NM_017645.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.491

Variant links:

Genes affected

HAUS6 (HGNC:25948): (HAUS augmin like complex subunit 6) The protein encoded by this gene is a subunit of the augmin complex. The augmin complex plays a role in microtubule attachment to the kinetochore and central spindle formation. This protein may have a role in efficient chromosome congression and segregation by promoting microtubule-dependent microtubule amplification. Pseudogenes of this gene are located on chromosomes 7 and 20. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Aug 2012]

HAUS6 links:

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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=0.036364168).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAUS6	NM_017645.5 link	c.2449G>A	p.Val817Met	missense_variant	Exon 16 of 17	ENST00000380502.8	NP_060115.3	Q7Z4H7-1
HAUS6	NM_001270890.2 link	c.2344G>A	p.Val782Met	missense_variant	Exon 16 of 17		NP_001257819.1	Q7Z4H7-3
HAUS6	XM_047423518.1 link	c.1798G>A	p.Val600Met	missense_variant	Exon 12 of 13		XP_047279474.1
HAUS6	XM_011517935.3 link	c.1156G>A	p.Val386Met	missense_variant	Exon 5 of 6		XP_011516237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAUS6	ENST00000380502.8 link	c.2449G>A	p.Val817Met	missense_variant	Exon 16 of 17	1	NM_017645.5	ENSP00000369871.3		Q7Z4H7-1
HAUS6	ENST00000380496.5 link	c.2041G>A	p.Val681Met	missense_variant	Exon 13 of 13	2		ENSP00000369865.1		Q5VY60

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

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:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000479

AC:

AN:

250694

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135622

show subpopulations

Gnomad AFR exome

AF:

0.000624

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461442

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000125

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.000386

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000143

Hom.:

Bravo

AF:

0.000106

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2449G>A (p.V817M) alteration is located in exon 16 (coding exon 16) of the HAUS6 gene. This alteration results from a G to A substitution at nucleotide position 2449, causing the valine (V) at amino acid position 817 to be replaced by a methionine (M). 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

0.094

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.74

CADD

Benign

2.5

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0013

T;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.53

T;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.036

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

N;.

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.33

N;N

REVEL

Benign

0.018

Sift

Benign

0.18

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.053

B;B

Vest4

0.060

MVP

0.17

MPC

0.026

ClinPred

0.0094

GERP RS

-0.57

Varity_R

0.014

gMVP

0.14

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

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