3-134559190-G-A

Position:

• chr3-134559190-G-A

Variant summary

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

The NM_001353108.3(CEP63):​c.1714G>A​(p.Glu572Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CEP63 NM_001353108.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57

Genes affected

CEP63 (HGNC:25815): (centrosomal protein 63) This gene encodes a protein with six coiled-coil domains. The protein is localized to the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. Several alternatively spliced transcript variants have been found, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

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=0.17643398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP63	NM_001353108.3	c.1714G>A	p.Glu572Lys	missense_variant	14/15	ENST00000675561.1	NP_001340037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP63	ENST00000675561.1	c.1714G>A	p.Glu572Lys	missense_variant	14/15		NM_001353108.3	ENSP00000502085	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 26, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T;T;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.055
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.69	.;.;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;M;M
MutationTaster	Benign	1.0	D;D;D;N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.53	N;.;N
REVEL	Benign	0.058
Sift	Benign	0.071	T;.;T
Sift4G	Benign	0.33	T;T;T
Polyphen		0.29	B;B;B
Vest4		0.46
MutPred		0.14		Gain of methylation at E572 (P = 0.0078);Gain of methylation at E572 (P = 0.0078);Gain of methylation at E572 (P = 0.0078);
MVP		0.45
MPC		0.034
ClinPred		0.46	T
GERP RS		3.9
Varity_R		0.10
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1553789251; hg19: chr3-134278032; COSMIC: COSV59675765; COSMIC: COSV59675765;