18-46105296-A-G

Position:

• chr18-46105296-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138443.4(HAUS1):​c.133A>G​(p.Arg45Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HAUS1 NM_138443.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.96

Genes affected

HAUS1 (HGNC:25174): (HAUS augmin like complex subunit 1) HAUS1 is 1 of 8 subunits of the 390-kD human augmin complex, or HAUS complex. The augmin complex was first identified in Drosophila, and its name comes from the Latin verb 'augmentare,' meaning 'to increase.' The augmin complex is a microtubule-binding complex involved in microtubule generation within the mitotic spindle and is vital to mitotic spindle assembly (Goshima et al., 2008 [PubMed 18443220]; Uehara et al., 2009 [PubMed 19369198]).[supplied by OMIM, Jun 2010]

HAUS1 (HGNC:):

ACMG classification

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=0.16155705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAUS1	NM_138443.4	c.133A>G	p.Arg45Gly	missense_variant	2/9	ENST00000282058.11	NP_612452.1
HAUS1	NR_026978.2	n.160A>G		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAUS1	ENST00000282058.11	c.133A>G	p.Arg45Gly	missense_variant	2/9	1	NM_138443.4	ENSP00000282058.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 09, 2024

The c.133A>G (p.R45G) alteration is located in exon 2 (coding exon 2) of the HAUS1 gene. This alteration results from a A to G substitution at nucleotide position 133, causing the arginine (R) at amino acid position 45 to be replaced by a glycine (G). 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	0.10
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T;.
Eigen	Benign	0.013
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.44	N
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.2	M;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.9	D;.;.
REVEL	Benign	0.082
Sift	Uncertain	0.020	D;.;.
Sift4G	Benign	0.064	T;T;T
Polyphen		0.15	B;.;.
Vest4		0.48
MutPred		0.28		Loss of stability (P = 0.0389);.;Loss of stability (P = 0.0389);
MVP		0.61
MPC		0.12
ClinPred		0.89	D
GERP RS		4.2
Varity_R		0.16
gMVP		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-43685262;