3-134559428-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001353108.3(CEP63):c.1952C>T(p.Ser651Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,609,348 control chromosomes in the GnomAD database, including 105,876 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 8213 hom., cov: 32)

Exomes 𝑓: 0.36 ( 97663 hom. )

Consequence

CEP63
NM_001353108.3 missense, splice_region

Scores

Splicing: ADA: 0.002098

Clinical Significance

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

Conservation

PhyloP100: 0.279

Publications

23 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.759179E-6).

BP6

Variant 3-134559428-C-T is Benign according to our data. Variant chr3-134559428-C-T is described in ClinVar as Benign. ClinVar VariationId is 128708.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP63	NM_001353108.3 link	c.1952C>T	p.Ser651Leu	missense_variant, splice_region_variant	Exon 14 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.1952C>T	p.Ser651Leu	missense_variant, splice_region_variant	Exon 14 of 15		NM_001353108.3	ENSP00000502085.1		Q96MT8-1

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44634

AN:

151946

Hom.:

8210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0791

Gnomad AMI

AF:

0.302

Gnomad AMR

AF:

0.439

Gnomad ASJ

AF:

0.324

Gnomad EAS

AF:

0.608

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.353

Gnomad OTH

AF:

0.315

GnomAD2 exomes

AF:

0.373

AC:

93089

AN:

249468

AF XY:

0.366

show subpopulations

Gnomad AFR exome

AF:

0.0746

Gnomad AMR exome

AF:

0.558

Gnomad ASJ exome

AF:

0.317

Gnomad EAS exome

AF:

0.617

Gnomad FIN exome

AF:

0.378

Gnomad NFE exome

AF:

0.352

Gnomad OTH exome

AF:

0.379

GnomAD4 exome

AF:

0.357

AC:

520881

AN:

1457284

Hom.:

97663

Cov.:

AF XY:

0.355

AC XY:

257121

AN XY:

725160

show subpopulations

African (AFR)

AF:

0.0662

AC:

2212

AN:

33412

American (AMR)

AF:

0.547

AC:

24326

AN:

44464

Ashkenazi Jewish (ASJ)

AF:

0.320

AC:

8339

AN:

26072

East Asian (EAS)

AF:

0.617

AC:

24480

AN:

39662

South Asian (SAS)

AF:

0.274

AC:

23549

AN:

85956

European-Finnish (FIN)

AF:

0.373

AC:

19872

AN:

53304

Middle Eastern (MID)

AF:

0.284

AC:

1633

AN:

5758

European-Non Finnish (NFE)

AF:

0.357

AC:

395471

AN:

1108462

Other (OTH)

AF:

0.349

AC:

20999

AN:

60194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

14441

28883

43324

57766

72207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12672

25344

38016

50688

63360

<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:

0.294

AC:

44644

AN:

152064

Hom.:

8213

Cov.:

AF XY:

0.299

AC XY:

22209

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0790

AC:

3278

AN:

41502

American (AMR)

AF:

0.439

AC:

6707

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.324

AC:

1126

AN:

3472

East Asian (EAS)

AF:

0.608

AC:

3146

AN:

5174

South Asian (SAS)

AF:

0.282

AC:

1357

AN:

4814

European-Finnish (FIN)

AF:

0.378

AC:

3994

AN:

10568

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.353

AC:

23996

AN:

67928

Other (OTH)

AF:

0.318

AC:

670

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1471

2942

4413

5884

7355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

448

896

1344

1792

2240

<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:

0.329

Hom.:

18594

Bravo

AF:

0.292

TwinsUK

AF:

0.352

AC:

1305

ALSPAC

AF:

0.354

AC:

1366

ESP6500AA

AF:

0.0912

AC:

402

ESP6500EA

AF:

0.358

AC:

3075

ExAC

AF:

0.357

AC:

43329

Asia WGS

AF:

0.407

AC:

1415

AN:

3478

EpiCase

AF:

0.346

EpiControl

AF:

0.350

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 10, 2018

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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Apr 25, 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

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0093

T;T;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.67

.;.;T

MetaRNN

Benign

0.0000078

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.68

N;N;N

PhyloP100

0.28

PrimateAI

Benign

0.34

PROVEAN

Benign

0.50

N;.;N

REVEL

Benign

0.045

Sift

Benign

0.33

T;.;T

Sift4G

Benign

0.30

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.025

MPC

0.027

ClinPred

0.0090

GERP RS

-2.9

Varity_R

0.041

gMVP

0.19

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0021

dbscSNV1_RF

Benign

0.042

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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