rs782732195

Variant names:

• chrX-153455675-T-A
• rs782732195
• NM_001385482.1:c.797A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001385482.1(HAUS7):​c.797A>T​(p.His266Leu) 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. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: HAUS7 NM_001385482.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55

Genes affected

HAUS7 (HGNC:32979): (HAUS augmin like complex subunit 7) This gene encodes a subunit of the augmin complex, which regulates centrosome and mitotic spindle integrity, and is necessary for the completion of cytokinesis. The encoded protein was identified by interaction with ubiquitin C-terminal hydrolase 37. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012]

TREX2 (HGNC:12270): (three prime repair exonuclease 2) This gene encodes a nuclear protein with 3' to 5' exonuclease activity. The encoded protein participates in double-stranded DNA break repair, and may interact with DNA polymerase delta. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34262007).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAUS7	NM_001385482.1	c.797A>T	p.His266Leu	missense_variant	Exon 8 of 10	ENST00000370211.10	NP_001372411.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAUS7	ENST00000370211.10	c.797A>T	p.His266Leu	missense_variant	Exon 8 of 10	1	NM_001385482.1	ENSP00000359230.6

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 24

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.827A>T (p.H276L) alteration is located in exon 8 (coding exon 8) of the HAUS7 gene. This alteration results from a A to T substitution at nucleotide position 827, causing the histidine (H) at amino acid position 276 to be replaced by a leucine (L). 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	0.25
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.26	T
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Benign	0.48	T
REVEL	Benign	0.17
Sift4G	Uncertain	0.035	D
Polyphen		0.78	P
Vest4		0.46
MutPred		0.28		Gain of helix (P = 0.0854);
MVP		0.93
MPC		0.59
ClinPred		0.96	D
GERP RS		3.8
Varity_R		0.41
gMVP		0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs782732195; hg19: chrX-152721133;