4-103158691-C-G

Position:

• chr4-103158691-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001813.3(CENPE):​c.2797G>C​(p.Asp933His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,840 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 0.0000066 (0 hom., cov: 32)
• Consequence: CENPE NM_001813.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.652

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]

ACMG classification

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=0.22171554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPE	NM_001813.3	c.2797G>C	p.Asp933His	missense_variant	23/49	ENST00000265148.9	NP_001804.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPE	ENST00000265148.9	c.2797G>C	p.Asp933His	missense_variant	23/49	2	NM_001813.3	ENSP00000265148.3
CENPE	ENST00000380026.8	c.2722G>C	p.Asp908His	missense_variant	22/47	1		ENSP00000369365.3

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151840 Hom.: 0 Cov.: 32

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151840 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74178

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: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T;.;.;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.65	T;T;T;T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Uncertain	0.11	D
MutationAssessor	Uncertain	2.2	M;.;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.5	D;D;.;N
REVEL	Uncertain	0.37
Sift	Benign	0.085	T;T;.;T
Sift4G	Benign	0.22	T;T;T;.
Polyphen		0.99	D;B;.;.
Vest4		0.21
MutPred		0.11		Gain of methylation at K931 (P = 0.1459);.;Gain of methylation at K931 (P = 0.1459);Gain of methylation at K931 (P = 0.1459);
MVP		0.74
MPC		0.22
ClinPred		0.90	D
GERP RS		0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.057
gMVP		0.20

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

Other links and lift over

dbSNP: rs144716013; hg19: chr4-104079848;