chr14-22948013-T-C

Variant names:

• chr14-22948013-T-C
• NM_001166269.2:c.563A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001166269.2(HAUS4):​c.563A>G​(p.Asp188Gly) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: HAUS4 NM_001166269.2 missense, splice_region
• Scores: Splicing: ADA: 0.002431
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.13
• Publications: 0 publications found

Genes affected

HAUS4 (HGNC:20163): (HAUS augmin like complex subunit 4) This gene encodes a subunit of the centrosome complex termed the human augmin complex. The encoded protein localizes to the spindle microtubules and may play a role in mitotic spindle assembly and maintenance of centrosome integrity during cell division. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 1. [provided by RefSeq, Oct 2009]

ENSG00000259132 (HGNC:):

PRMT5-DT (HGNC:55482): (PRMT5 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3099141).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAUS4	NM_001166269.2	c.563A>G	p.Asp188Gly	missense_variant, splice_region_variant	Exon 7 of 10	ENST00000541587.6	NP_001159741.1
HAUS4	NM_017815.3	c.563A>G	p.Asp188Gly	missense_variant, splice_region_variant	Exon 7 of 10		NP_060285.2
HAUS4	NM_001166270.2	c.428A>G	p.Asp143Gly	missense_variant, splice_region_variant	Exon 6 of 9		NP_001159742.1
PRMT5-DT	NR_110002.1	n.195-6318T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAUS4	ENST00000541587.6	c.563A>G	p.Asp188Gly	missense_variant, splice_region_variant	Exon 7 of 10	1	NM_001166269.2	ENSP00000441026.1
ENSG00000259132	ENST00000555074.1	c.50A>G	p.Asp17Gly	missense_variant, splice_region_variant	Exon 2 of 5	2		ENSP00000450856.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 23, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.563A>G (p.D188G) alteration is located in exon 7 (coding exon 6) of the HAUS4 gene. This alteration results from a A to G substitution at nucleotide position 563, causing the aspartic acid (D) at amino acid position 188 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	0.12
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.081	.;T;T;.;.;.;T
Eigen	Benign	0.033
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.56	T;.;T;.;.;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.31	T;T;T;T;T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.3	.;M;M;.;.;.;.
PhyloP100		4.1
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-2.1	N;N;N;N;N;N;D
REVEL	Benign	0.14
Sift	Uncertain	0.0030	D;D;D;D;D;D;D
Sift4G	Benign	0.17	T;T;T;T;T;T;.
Polyphen		0.085, 0.31	.;B;B;B;B;B;.
Vest4		0.40
MutPred		0.30		.;Gain of catalytic residue at Y183 (P = 0.0198);Gain of catalytic residue at Y183 (P = 0.0198);.;.;.;Gain of catalytic residue at Y183 (P = 0.0198);
MVP		0.67
MPC		0.29
ClinPred		0.96	D
GERP RS		5.2
Varity_R		0.17
gMVP		0.28
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0024
dbscSNV1_RF	Benign	0.016
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

hg19: chr14-23417222;