Variant rs144716013 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001813.3(CENPE):c.2797G>T(p.Asp933Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,612,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

CENPE
NM_001813.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.652

Variant links:

Genes affected

CENPE (HGNC:1856): (centromere protein E) Centrosome-associated protein E (CENPE) is a kinesin-like motor protein that accumulates in the G2 phase of the cell cycle. Unlike other centrosome-associated proteins, it is not present during interphase and first appears at the centromere region of chromosomes during prometaphase. This protein is required for stable spindle microtubule capture at kinetochores which is a necessary step in chromosome alignment during prometaphase. This protein also couples chromosome position to microtubule depolymerizing activity. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. [provided by RefSeq, Nov 2014]

CENPE links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009747863).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPE	NM_001813.3 linkuse as main transcript	c.2797G>T	p.Asp933Tyr	missense_variant	23/49	ENST00000265148.9	NP_001804.2	Q02224-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPE	ENST00000265148.9 linkuse as main transcript	c.2797G>T	p.Asp933Tyr	missense_variant	23/49	2	NM_001813.3	ENSP00000265148.3		Q02224-1
CENPE	ENST00000380026.8 linkuse as main transcript	c.2722G>T	p.Asp908Tyr	missense_variant	22/47	1		ENSP00000369365.3		Q02224-3

Frequencies

GnomAD3 genomes

AF:

0.000290

AC:

AN:

151840

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00406

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000440

AC:

110

AN:

250284

Hom.:

AF XY:

0.000488

AC XY:

AN XY:

135328

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00440

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.000155

AC:

226

AN:

1460626

Hom.:

Cov.:

AF XY:

0.000171

AC XY:

124

AN XY:

726606

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00362

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000290

AC:

AN:

151840

Hom.:

Cov.:

AF XY:

0.000512

AC XY:

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00406

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000210

Hom.:

ExAC

AF:

0.000346

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.57

D;.;.;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.66

T;T;T;T

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.0097

T;T;T;T

MetaSVM

Uncertain

0.14

MutationAssessor

Uncertain

2.2

M;.;.;.

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.7

D;D;.;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.011

D;D;.;D

Sift4G

Uncertain

0.029

D;D;D;.

Polyphen

0.98

D;P;.;.

Vest4

0.28

MutPred

0.11

Gain of phosphorylation at D933 (P = 0.0587);.;Gain of phosphorylation at D933 (P = 0.0587);Gain of phosphorylation at D933 (P = 0.0587);

MVP

0.81

MPC

0.26

ClinPred

0.43

GERP RS

0.28

Varity_R

0.14

gMVP

0.29

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over