14-22946641-A-G

Variant names:

• chr14-22946641-A-G
• rs200660231
• NM_001166269.2:c.976T>C

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.976T>C​(p.Ser326Pro) 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. 13/21 in silico tools predict 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. S326A) 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: 0.363
• 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=0.1338729).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAUS4	NM_001166269.2	c.976T>C	p.Ser326Pro	missense_variant	Exon 10 of 10	ENST00000541587.6	NP_001159741.1
HAUS4	NM_017815.3	c.976T>C	p.Ser326Pro	missense_variant	Exon 10 of 10		NP_060285.2
HAUS4	NM_001166270.2	c.841T>C	p.Ser281Pro	missense_variant	Exon 9 of 9		NP_001159742.1
PRMT5-DT	NR_110002.1	n.195-7690A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAUS4	ENST00000541587.6	c.976T>C	p.Ser326Pro	missense_variant	Exon 10 of 10	1	NM_001166269.2	ENSP00000441026.1
ENSG00000259132	ENST00000555074.1	c.463T>C	p.Ser155Pro	missense_variant	Exon 5 of 5	2		ENSP00000450856.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	.;T;T;.;.;.;.
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.76	T;.;T;.;T;.;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.13	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.75	.;N;N;.;.;.;.
PhyloP100		0.36
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.6	D;D;D;N;D;N;N
REVEL	Benign	0.056
Sift	Uncertain	0.014	D;D;D;D;D;D;D
Sift4G	Benign	0.21	T;T;T;T;T;T;T
Polyphen		0.26, 0.0	.;B;B;B;B;B;B
Vest4		0.25
MutPred		0.33		.;Gain of loop (P = 0.0121);Gain of loop (P = 0.0121);.;.;.;.;
MVP		0.37
MPC		0.31
ClinPred		0.85	D
GERP RS		0.69
Varity_R		0.34
gMVP		0.60
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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

dbSNP: rs200660231; hg19: chr14-23415850;