NM_001813.3:c.4791A>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001813.3(CENPE):c.4791A>C(p.Arg1597Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00528 in 1,611,142 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R1597R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0042 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0054 ( 29 hom. )

Consequence

CENPE
NM_001813.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -1.06

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 Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038477182).

BP6

Variant 4-103145116-T-G is Benign according to our data. Variant chr4-103145116-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 434695.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPE	NM_001813.3 link	c.4791A>C	p.Arg1597Ser	missense_variant	Exon 32 of 49	ENST00000265148.9	NP_001804.2	Q02224-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CENPE	ENST00000265148.9 link	c.4791A>C	p.Arg1597Ser	missense_variant	Exon 32 of 49	2	NM_001813.3	ENSP00000265148.3	Q02224-1
CENPE	ENST00000380026.8 link	c.4716A>C	p.Arg1572Ser	missense_variant	Exon 31 of 47	1		ENSP00000369365.3	Q02224-3
CENPE	ENST00000515478.1 link	n.*187A>C		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00424

AC:

645

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00511

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00700

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00410

AC:

1024

AN:

249958

Hom.:

AF XY:

0.00443

AC XY:

599

AN XY:

135180

show subpopulations

Gnomad AFR exome

AF:

0.000801

Gnomad AMR exome

AF:

0.00300

Gnomad ASJ exome

AF:

0.00220

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000855

Gnomad FIN exome

AF:

0.000884

Gnomad NFE exome

AF:

0.00721

Gnomad OTH exome

AF:

0.00410

GnomAD4 exome

AF:

0.00539

AC:

7864

AN:

1458886

Hom.:

Cov.:

AF XY:

0.00539

AC XY:

3914

AN XY:

725716

show subpopulations

Gnomad4 AFR exome

AF:

0.000811

Gnomad4 AMR exome

AF:

0.00349

Gnomad4 ASJ exome

AF:

0.00265

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.000841

Gnomad4 FIN exome

AF:

0.000921

Gnomad4 NFE exome

AF:

0.00648

Gnomad4 OTH exome

AF:

0.00463

GnomAD4 genome

AF:

0.00423

AC:

644

AN:

152256

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

292

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00504

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000848

Gnomad4 NFE

AF:

0.00700

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00617

Hom.:

Bravo

AF:

0.00465

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00686

AC:

ExAC

AF:

0.00418

AC:

507

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CENPE: BP4, BS2 -

not specified

Uncertain:1

Feb 20, 2017

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

5.0

DANN

Benign

0.89

DEOGEN2

Benign

0.050

T;.;.

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.60

T;T;T

MetaRNN

Benign

0.0038

T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.1

M;.;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.1

N;N;.

REVEL

Benign

0.23

Sift

Benign

0.41

T;T;.

Sift4G

Benign

0.094

T;T;T

Polyphen

0.97

D;D;.

Vest4

0.13

MutPred

0.13

Gain of phosphorylation at R1597 (P = 0.0244);.;Gain of phosphorylation at R1597 (P = 0.0244);

MVP

0.80

MPC

0.043

ClinPred

0.020

GERP RS

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.052

gMVP

0.074

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over