9-19058329-A-C

Variant names:

• chr9-19058329-A-C
• rs370946839
• NM_017645.5:c.2438T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017645.5(HAUS6):​c.2438T>G​(p.Leu813Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L813P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HAUS6 NM_017645.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05559975).

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.2438T>G	p.Leu813Arg	missense	Exon 16 of 17	NP_060115.3
	HAUS6	NM_001270890.2		c.2333T>G	p.Leu778Arg	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.2438T>G	p.Leu813Arg	missense	Exon 16 of 17	ENSP00000369871.3	Q7Z4H7-1
	HAUS6	ENST00000888740.1		c.2624T>G	p.Leu875Arg	missense	Exon 17 of 18	ENSP00000558799.1
	HAUS6	ENST00000888738.1		c.2489T>G	p.Leu830Arg	missense	Exon 17 of 18	ENSP00000558797.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461520 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727074

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111724

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	10
DANN	Benign	0.63
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.28
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.0070
Sift	Benign	0.60	T
Sift4G	Benign	0.58	T
Polyphen		0.42	B
Vest4		0.15
MutPred		0.24		Gain of methylation at L813 (P = 0.0429)
MVP		0.19
MPC		0.049
ClinPred		0.042	T
GERP RS		1.2
Varity_R		0.040
gMVP		0.17
Mutation Taster		=94/6	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: rs370946839; hg19: chr9-19058327;