14-22948007-T-A

Variant names:

• chr14-22948007-T-A
• rs149652875
• NM_001166269.2:c.569A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001166269.2(HAUS4):​c.569A>T​(p.Asp190Val) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D190A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: HAUS4 NM_001166269.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.60
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22101286).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAUS4	NM_001166269.2	c.569A>T	p.Asp190Val	missense_variant	Exon 7 of 10	ENST00000541587.6	NP_001159741.1
HAUS4	NM_017815.3	c.569A>T	p.Asp190Val	missense_variant	Exon 7 of 10		NP_060285.2
HAUS4	NM_001166270.2	c.434A>T	p.Asp145Val	missense_variant	Exon 6 of 9		NP_001159742.1
PRMT5-DT	NR_110002.1	n.195-6324T>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAUS4	ENST00000541587.6	c.569A>T	p.Asp190Val	missense_variant	Exon 7 of 10	1	NM_001166269.2	ENSP00000441026.1
ENSG00000259132	ENST00000555074.1	c.56A>T	p.Asp19Val	missense_variant	Exon 2 of 5	2		ENSP00000450856.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000413 AC: 1 AN: 242252 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	.;T;T;.;.;.;T
Eigen	Benign	0.043
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.88	D;.;D;.;.;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.22	T;T;T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.2	.;M;M;.;.;.;.
PhyloP100		2.6
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.0	D;D;D;D;D;D;D
REVEL	Benign	0.13
Sift	Uncertain	0.0070	D;D;D;D;D;D;D
Sift4G	Benign	0.18	T;D;D;D;D;D;.
Polyphen		0.79, 0.40	.;P;P;B;B;B;.
Vest4		0.37
MutPred		0.23		.;Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);.;.;.;Gain of helix (P = 0.0425);
MVP		0.68
MPC		0.87
ClinPred		0.91	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.28
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs149652875; hg19: chr14-23417216;