Variant chr3-134559428-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 16/22 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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 128708.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-134559428-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
CEP63	NM_001353108.3 linkuse as main transcript	c.1952C>T	p.Ser651Leu	missense_variant, splice_region_variant	14/15	ENST00000675561.1	NP_001340037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP63	ENST00000675561.1 linkuse as main transcript	c.1952C>T	p.Ser651Leu	missense_variant, splice_region_variant	14/15		NM_001353108.3	ENSP00000502085	A1	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

GnomAD3 exomes

AF:

0.373

AC:

93089

AN:

249468

Hom.:

19536

AF XY:

0.366

AC XY:

49421

AN XY:

134962

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 SAS exome

AF:

0.268

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

Gnomad4 AFR exome

AF:

0.0662

Gnomad4 AMR exome

AF:

0.547

Gnomad4 ASJ exome

AF:

0.320

Gnomad4 EAS exome

AF:

0.617

Gnomad4 SAS exome

AF:

0.274

Gnomad4 FIN exome

AF:

0.373

Gnomad4 NFE exome

AF:

0.357

Gnomad4 OTH exome

AF:

0.349

GnomAD4 genome

AF:

0.294

AC:

44644

AN:

152064

Hom.:

8213

Cov.:

AF XY:

0.299

AC XY:

22209

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0790

Gnomad4 AMR

AF:

0.439

Gnomad4 ASJ

AF:

0.324

Gnomad4 EAS

AF:

0.608

Gnomad4 SAS

AF:

0.282

Gnomad4 FIN

AF:

0.378

Gnomad4 NFE

AF:

0.353

Gnomad4 OTH

AF:

0.318

Alfa

AF:

0.340

Hom.:

11013

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 25, 2013

- -

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

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

MutationTaster

Benign

6.0e-8

P;P;P;P;P

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over