18-46105331-G-T

Position:

• chr18-46105331-G-T

Variant summary

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

The NM_138443.4(HAUS1):​c.168G>T​(p.Glu56Asp) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HAUS1 NM_138443.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.0850

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=0.2279051).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAUS1	NM_138443.4	c.168G>T	p.Glu56Asp	missense_variant	2/9	ENST00000282058.11	NP_612452.1
HAUS1	NR_026978.2	n.195G>T		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAUS1	ENST00000282058.11	c.168G>T	p.Glu56Asp	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: no assertion criteria provided

Submissions by phenotype

HAUS1-related condition Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 26, 2024

The HAUS1 c.168G>T variant is predicted to result in the amino acid substitution p.Glu56Asp. To our knowledge, this variant has not been reported in the literature or in gnomAD, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.061	T;T;.
Eigen	Benign	0.11
Eigen_PC	Benign	-0.013
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Pathogenic	3.0	M;.;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.8	N;.;.
REVEL	Benign	0.20
Sift	Benign	0.11	T;.;.
Sift4G	Uncertain	0.036	D;D;T
Polyphen		0.99	D;.;.
Vest4		0.37
MutPred		0.10		Loss of methylation at K59 (P = 0.0798);.;Loss of methylation at K59 (P = 0.0798);
MVP		0.34
MPC		0.072
ClinPred		0.88	D
GERP RS		0.96
Varity_R		0.13
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr18-43685297;