9-19057993-G-A

Variant names:

• chr9-19057993-G-A
• NM_017645.5:c.2774C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017645.5(HAUS6):​c.2774C>T​(p.Ala925Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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)
• Consequence: HAUS6 NM_017645.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.23
• Publications: 0 publications found

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]

ACMG classification

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=0.14482409).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017645.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAUS6	NM_017645.5	MANE Select	c.2774C>T	p.Ala925Val	missense	Exon 16 of 17	NP_060115.3
	HAUS6	NM_001270890.2		c.2669C>T	p.Ala890Val	missense	Exon 16 of 17	NP_001257819.1	Q7Z4H7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAUS6	ENST00000380502.8	TSL:1 MANE Select	c.2774C>T	p.Ala925Val	missense	Exon 16 of 17	ENSP00000369871.3	Q7Z4H7-1
	HAUS6	ENST00000888740.1		c.2960C>T	p.Ala987Val	missense	Exon 17 of 18	ENSP00000558799.1
	HAUS6	ENST00000888738.1		c.2825C>T	p.Ala942Val	missense	Exon 17 of 18	ENSP00000558797.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.061
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.2
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.058
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.010	D
Polyphen		0.066	B
Vest4		0.084
MutPred		0.34		Gain of sheet (P = 0.0049)
MVP		0.32
MPC		0.026
ClinPred		0.47	T
GERP RS		5.5
Varity_R		0.13
gMVP		0.11
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr9-19057991;