rs9827878

chr3-134507127-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001353108.3(CEP63):c.63T>C(p.Cys21=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,612,436 control chromosomes in the GnomAD database, including 22,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (1922 hom., cov: 31)
  • Exomes 𝑓: 0.17 (20542 hom.)
• Consequence: CEP63 NM_001353108.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.66

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 Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 3-134507127-T-C is Benign according to our data. Variant chr3-134507127-T-C is described in ClinVar as [Benign]. Clinvar id is 128712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.65 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP63	NM_001353108.3	c.63T>C	p.Cys21=	synonymous_variant	3/15	ENST00000675561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP63	ENST00000675561.1	c.63T>C	p.Cys21=	synonymous_variant	3/15		NM_001353108.3	A1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23833 AN: 151820 Hom.: 1919 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.142

GnomAD3 exomes AF: 0.171 AC: 42982 AN: 251218 Hom.: 3889 AF XY: 0.169 AC XY: 22999 AN XY: 135798

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.167

Gnomad ASJ exome AF: 0.102

Gnomad EAS exome AF: 0.217

Gnomad SAS exome AF: 0.176

Gnomad FIN exome AF: 0.231

Gnomad NFE exome AF: 0.166

Gnomad OTH exome AF: 0.153

GnomAD4 exome AF: 0.166 AC: 241908 AN: 1460498 Hom.: 20542 Cov.: 32 AF XY: 0.166 AC XY: 120377 AN XY: 726608

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.162

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.181

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.234

Gnomad4 NFE exome AF: 0.164

Gnomad4 OTH exome AF: 0.161

GnomAD4 genome AF: 0.157 AC: 23840 AN: 151938 Hom.: 1922 Cov.: 31 AF XY: 0.159 AC XY: 11788 AN XY: 74222

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.140

Alfa AF: 0.159 Hom.: 3915

Bravo AF: 0.152

Asia WGS AF: 0.210 AC: 731 AN: 3478

EpiCase AF: 0.158

EpiControl AF: 0.152

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 15, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	9.6
Dann	Benign	0.86

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: rs9827878; hg19: chr3-134225969; COSMIC: COSV59676362; COSMIC: COSV59676362;