dbSNP rs9827878: CEP63:p.Cys21Cys (chr3-134507127-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001353108.3(CEP63):c.63T>C(p.Cys21Cys) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.66

Publications

18 publications found

Variant links:

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

CEP63 links:

ENSG00000288700 (HGNC:):

ENSG00000288700 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
CEP63	NM_001353108.3 link	c.63T>C	p.Cys21Cys	synonymous_variant	Exon 3 of 15	ENST00000675561.1	NP_001340037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP63	ENST00000675561.1 link	c.63T>C	p.Cys21Cys	synonymous_variant	Exon 3 of 15		NM_001353108.3	ENSP00000502085.1		Q96MT8-1

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23833

AN:

151820

Hom.:

1919

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.171

AC:

42982

AN:

251218

AF XY:

0.169

show subpopulations

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 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.:

AF XY:

0.166

AC XY:

120377

AN XY:

726608

show subpopulations

African (AFR)

AF:

0.129

AC:

4308

AN:

33442

American (AMR)

AF:

0.162

AC:

7248

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

2618

AN:

26110

East Asian (EAS)

AF:

0.181

AC:

7161

AN:

39614

South Asian (SAS)

AF:

0.176

AC:

15206

AN:

86198

European-Finnish (FIN)

AF:

0.234

AC:

12477

AN:

53396

Middle Eastern (MID)

AF:

0.123

AC:

710

AN:

5762

European-Non Finnish (NFE)

AF:

0.164

AC:

182464

AN:

1110916

Other (OTH)

AF:

0.161

AC:

9716

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

9248

18495

27743

36990

46238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6516

13032

19548

26064

32580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.157

AC:

23840

AN:

151938

Hom.:

1922

Cov.:

AF XY:

0.159

AC XY:

11788

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.128

AC:

5304

AN:

41454

American (AMR)

AF:

0.149

AC:

2273

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

365

AN:

3472

East Asian (EAS)

AF:

0.204

AC:

1052

AN:

5160

South Asian (SAS)

AF:

0.182

AC:

876

AN:

4808

European-Finnish (FIN)

AF:

0.224

AC:

2361

AN:

10518

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.165

AC:

11185

AN:

67964

Other (OTH)

AF:

0.140

AC:

296

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

989

1978

2967

3956

4945

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.160

Hom.:

7795

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.6

(source)

DANN

Benign

0.86

PhyloP100

1.7

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over