chr3-134559190-G-A

Variant names:

• chr3-134559190-G-A
• rs1553789251
• NM_001353108.3:c.1714G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025180.5(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. 13/22 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_025180.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57
• Publications: 0 publications found

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]

CEP63 Gene-Disease associations (from GenCC):

• Seckel syndrome 6

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000288700 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17643398).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025180.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP63	NM_001353108.3	MANE Select	c.1714G>A	p.Glu572Lys	missense	Exon 14 of 15	NP_001340037.1
	CEP63	NM_025180.5		c.1714G>A	p.Glu572Lys	missense	Exon 15 of 16	NP_079456.2
	CEP63	NM_001353109.1		c.1576G>A	p.Glu526Lys	missense	Exon 13 of 14	NP_001340038.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP63	ENST00000675561.1	MANE Select	c.1714G>A	p.Glu572Lys	missense	Exon 14 of 15	ENSP00000502085.1
	CEP63	ENST00000383229.8	TSL:1	c.1468-2187G>A		intron	N/A	ENSP00000372716.3
	CEP63	ENST00000332047.10	TSL:1	c.1330-2187G>A		intron	N/A	ENSP00000328382.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		4.6
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.058
Sift	Benign	0.071	T
Sift4G	Benign	0.33	T
Polyphen		0.29	B
Vest4		0.46
MutPred		0.14		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
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs1553789251; hg19: chr3-134278032; COSMIC: COSV59675765; COSMIC: COSV59675765;