Genetic Variant HAUS6:p.Arg897His (chr9-19058077-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.2690G>A(p.Arg897His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R897C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

HAUS6
NM_017645.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.334

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=0.024487227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAUS6	NM_017645.5 link	c.2690G>A	p.Arg897His	missense_variant	Exon 16 of 17	ENST00000380502.8	NP_060115.3	Q7Z4H7-1
HAUS6	NM_001270890.2 link	c.2585G>A	p.Arg862His	missense_variant	Exon 16 of 17		NP_001257819.1	Q7Z4H7-3
HAUS6	XM_047423518.1 link	c.2039G>A	p.Arg680His	missense_variant	Exon 12 of 13		XP_047279474.1
HAUS6	XM_011517935.3 link	c.1397G>A	p.Arg466His	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.2690G>A	p.Arg897His	missense_variant	Exon 16 of 17	1	NM_017645.5	ENSP00000369871.3		Q7Z4H7-1
HAUS6	ENST00000380496.5 link	c.2282G>A	p.Arg761His	missense_variant	Exon 13 of 13	2		ENSP00000369865.1		Q5VY60

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000557

AC:

AN:

251444

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000707

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461676

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2690G>A (p.R897H) 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 2690, causing the arginine (R) at amino acid position 897 to be replaced by a histidine (H). 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

0.076

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.2

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0018

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.0047

MetaRNN

Benign

0.024

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.1

M;.

PrimateAI

Benign

0.18

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.011

Sift

Benign

0.12

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.0010

B;B

Vest4

0.044

MutPred

0.25

Loss of MoRF binding (P = 0.0368);.;

MVP

0.030

MPC

0.029

ClinPred

0.028

GERP RS

-4.5

Varity_R

0.033

gMVP

0.10

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