9-19058422-T-C

Variant names:

• chr9-19058422-T-C
• rs776427843
• NM_017645.5:c.2345A>G

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.2345A>G​(p.Glu782Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,609,844 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HAUS6 NM_017645.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.75
• Publications: 1 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=0.21853763).

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.2345A>G	p.Glu782Gly	missense	Exon 16 of 17	NP_060115.3
	HAUS6	NM_001270890.2		c.2240A>G	p.Glu747Gly	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.2345A>G	p.Glu782Gly	missense	Exon 16 of 17	ENSP00000369871.3	Q7Z4H7-1
	HAUS6	ENST00000888740.1		c.2531A>G	p.Glu844Gly	missense	Exon 17 of 18	ENSP00000558799.1
	HAUS6	ENST00000888738.1		c.2396A>G	p.Glu799Gly	missense	Exon 17 of 18	ENSP00000558797.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000802 AC: 2 AN: 249332 AF XY: 0.00

Gnomad AFR exome AF: 0.000130

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000137 AC: 2 AN: 1457708 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725384

African (AFR) AF: 0.0000606 AC: 2 AN: 32978

American (AMR) AF: 0.00 AC: 0 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108760

Other (OTH) AF: 0.00 AC: 0 AN: 60240

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152136 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74316

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000121 AC: 5 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000000533362), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

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	0.23
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.060	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.8
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.78	P
Vest4		0.37
MutPred		0.26		Gain of sheet (P = 0.0125)
MVP		0.59
MPC		0.057
ClinPred		0.95	D
GERP RS		4.4
Varity_R		0.57
gMVP		0.35
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs776427843; hg19: chr9-19058420;