Genetic Variant NM_017645.5:c.2354G>T (chr9-19058413-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017645.5(HAUS6):c.2354G>T(p.Gly785Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,822 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HAUS6
NM_017645.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.255

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21774647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAUS6	NM_017645.5 link	c.2354G>T	p.Gly785Val	missense_variant	Exon 16 of 17	ENST00000380502.8	NP_060115.3	Q7Z4H7-1
HAUS6	NM_001270890.2 link	c.2249G>T	p.Gly750Val	missense_variant	Exon 16 of 17		NP_001257819.1	Q7Z4H7-3
HAUS6	XM_047423518.1 link	c.1703G>T	p.Gly568Val	missense_variant	Exon 12 of 13		XP_047279474.1
HAUS6	XM_011517935.3 link	c.1061G>T	p.Gly354Val	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.2354G>T	p.Gly785Val	missense_variant	Exon 16 of 17	1	NM_017645.5	ENSP00000369871.3		Q7Z4H7-1
HAUS6	ENST00000380496.5 link	c.1946G>T	p.Gly649Val	missense_variant	Exon 13 of 13	2		ENSP00000369865.1		Q5VY60

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249996

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135460

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460822

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726754

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2354G>T (p.G785V) alteration is located in exon 16 (coding exon 16) of the HAUS6 gene. This alteration results from a G to T substitution at nucleotide position 2354, causing the glycine (G) at amino acid position 785 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

0.20

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.077

T;T

Eigen

Benign

0.18

Eigen_PC

Benign

0.075

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.9

L;.

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-4.5

D;D

REVEL

Benign

0.058

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

D;P

Vest4

0.36

MutPred

0.34

Gain of sheet (P = 0.0049);.;

MVP

0.32

MPC

0.22

ClinPred

0.97

GERP RS

3.5

Varity_R

0.39

gMVP

0.23

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