rs771325556

Variant names:

• chr14-22947214-C-G
• rs771325556
• NM_001166269.2:c.865G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-22947214-C-G
• chr14-22947214-C-T

Variant summary

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

The NM_001166269.2(HAUS4):​c.865G>C​(p.Asp289His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. D289N) 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: 4.47
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAUS4	NM_001166269.2	c.865G>C	p.Asp289His	missense_variant	Exon 9 of 10	ENST00000541587.6	NP_001159741.1
HAUS4	NM_017815.3	c.865G>C	p.Asp289His	missense_variant	Exon 9 of 10		NP_060285.2
HAUS4	NM_001166270.2	c.730G>C	p.Asp244His	missense_variant	Exon 8 of 9		NP_001159742.1
PRMT5-DT	NR_110002.1	n.195-7117C>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAUS4	ENST00000541587.6	c.865G>C	p.Asp289His	missense_variant	Exon 9 of 10	1	NM_001166269.2	ENSP00000441026.1
ENSG00000259132	ENST00000555074.1	c.352G>C	p.Asp118His	missense_variant	Exon 4 of 5	2		ENSP00000450856.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	.;T;T;.;.;.;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;.;D;.;D;.;D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.64	D;D;D;D;D;D;D
MetaSVM	Benign	-0.28	T
MutationAssessor	Uncertain	2.4	.;M;M;.;.;.;.
PhyloP100		4.5
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-4.5	D;D;D;D;D;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0040	D;D;D;D;D;D;D
Sift4G	Uncertain	0.014	D;D;D;D;D;D;D
Polyphen		1.0, 1.0	.;D;D;D;D;D;D
Vest4		0.73
MutPred		0.36		.;Gain of catalytic residue at Y291 (P = 0.0341);Gain of catalytic residue at Y291 (P = 0.0341);.;.;.;.;
MVP		0.79
MPC		0.88
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.54
gMVP		0.53
Mutation Taster		=68/32	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: rs771325556; hg19: chr14-23416423;