rs144716013

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PM2PM5BP4_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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D933N) has been classified as Likely pathogenic.

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

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

Seckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive primary microcephaly
Inheritance: AR Classification: LIMITED Submitted by: ClinGen
microcephaly 13, primary, autosomal recessive
Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina

CENPE links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr4-103158691-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 157497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPE	NM_001813.3 link	c.2797G>T	p.Asp933Tyr	missense_variant	Exon 23 of 49	ENST00000265148.9	NP_001804.2	Q02224-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPE	ENST00000265148.9 link	c.2797G>T	p.Asp933Tyr	missense_variant	Exon 23 of 49	2	NM_001813.3	ENSP00000265148.3		Q02224-1
CENPE	ENST00000380026.8 link	c.2722G>T	p.Asp908Tyr	missense_variant	Exon 22 of 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

GnomAD2 exomes

AF:

0.000440

AC:

110

AN:

250284

AF XY:

0.000488

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 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

African (AFR)

AF:

0.000150

AC:

AN:

33368

American (AMR)

AF:

0.00

AC:

AN:

44558

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39624

South Asian (SAS)

AF:

0.00

AC:

AN:

86092

European-Finnish (FIN)

AF:

0.00362

AC:

193

AN:

53318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1111474

Other (OTH)

AF:

0.000232

AC:

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000290

AC:

AN:

151840

Hom.:

Cov.:

AF XY:

0.000512

AC XY:

AN XY:

74178

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41408

American (AMR)

AF:

0.00

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00406

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67780

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000252

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

(source)

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;.;.;.

PhyloP100

0.65

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

Mutation Taster

=82/18

polymorphism

(source)

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

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rs144716013

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over