4-103110949-C-T
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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
NM_001813.3 missense
Scores
1
11
7
Clinical Significance
Conservation
PhyloP100: 3.84
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]
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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 |
---|---|---|---|---|---|---|---|---|
CENPE | NM_001813.3 | c.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 |
---|---|---|---|---|---|---|---|---|---|---|
CENPE | ENST00000265148.9 | c.7603G>A | p.Gly2535Ser | missense_variant | 47/49 | 2 | NM_001813.3 | ENSP00000265148 | A2 | |
CENPE | ENST00000380026.8 | c.7240G>A | p.Gly2414Ser | missense_variant | 45/47 | 1 | ENSP00000369365 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 151988Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000762 AC: 19AN: 249214Hom.: 0 AF XY: 0.0000816 AC XY: 11AN XY: 134768
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GnomAD4 exome AF: 0.0000425 AC: 62AN: 1458712Hom.: 0 Cov.: 30 AF XY: 0.0000400 AC XY: 29AN XY: 725760
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 151988Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74234
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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 submitter | clinical testing | GeneDx | Mar 01, 2023 | In 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;.
REVEL
Benign
Sift
Uncertain
D;D;.
Sift4G
Pathogenic
D;D;D
Polyphen
D;D;.
Vest4
MutPred
Loss of glycosylation at S2534 (P = 0.0239);.;.;
MVP
MPC
ClinPred
T
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at