4-103110949-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001813.3(CENPE):​c.7603G>A​(p.Gly2535Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000416 in 1,610,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

CENPE
NM_001813.3 missense

Scores

1
11
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.84
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13083196).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CENPENM_001813.3 linkuse as main transcriptc.7603G>A p.Gly2535Ser missense_variant 47/49 ENST00000265148.9 NP_001804.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CENPEENST00000265148.9 linkuse as main transcriptc.7603G>A p.Gly2535Ser missense_variant 47/492 NM_001813.3 ENSP00000265148 A2Q02224-1
CENPEENST00000380026.8 linkuse as main transcriptc.7240G>A p.Gly2414Ser missense_variant 45/471 ENSP00000369365 P2Q02224-3

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
151988
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000578
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000622
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000762
AC:
19
AN:
249214
Hom.:
0
AF XY:
0.0000816
AC XY:
11
AN XY:
134768
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000896
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000198
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000354
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000425
AC:
62
AN:
1458712
Hom.:
0
Cov.:
30
AF XY:
0.0000400
AC XY:
29
AN XY:
725760
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.000847
Gnomad4 EAS exome
AF:
0.000127
Gnomad4 SAS exome
AF:
0.000210
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000901
Gnomad4 OTH exome
AF:
0.0000996
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
151988
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74234
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000578
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000622
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000900
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.0000988
AC:
12
EpiCase
AF:
0.0000550
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxMar 01, 2023In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in an individual with West syndrome in published literature, however this individual also harbored variants in several other genes (Peng et al., 2018); This variant is associated with the following publications: (PMID: 29667327) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.56
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.32
T;.;.
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Uncertain
0.86
D;D;D
M_CAP
Uncertain
0.19
D
MetaRNN
Benign
0.13
T;T;T
MetaSVM
Benign
-0.59
T
MutationAssessor
Uncertain
2.2
M;.;.
MutationTaster
Benign
0.92
N;N
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-3.0
D;D;.
REVEL
Benign
0.29
Sift
Uncertain
0.0010
D;D;.
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.45
MutPred
0.30
Loss of glycosylation at S2534 (P = 0.0239);.;.;
MVP
0.79
MPC
0.28
ClinPred
0.48
T
GERP RS
3.4
Varity_R
0.17
gMVP
0.27

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.

Other links and lift over

dbSNP: rs756483643; hg19: chr4-104032106; COSMIC: COSV54387672; API