13-24892817-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018451.5(CENPJ):c.3042A>G(p.Glu1014Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,610,908 control chromosomes in the GnomAD database, including 236,901 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18933 hom., cov: 29)

Exomes 𝑓: 0.54 ( 217968 hom. )

Consequence

CENPJ
NM_018451.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 0.210

Variant links:

Genes affected

CENPJ (HGNC:17272): (centromere protein J) This gene encodes a protein that belongs to the centromere protein family. During cell division, this protein plays a structural role in the maintenance of centrosome integrity and normal spindle morphology, and it is involved in microtubule disassembly at the centrosome. This protein can function as a transcriptional coactivator in the Stat5 signaling pathway, and also as a coactivator of NF-kappaB-mediated transcription, likely via its interaction with the coactivator p300/CREB-binding protein. Mutations in this gene are associated with primary autosomal recessive microcephaly, a disorder characterized by severely reduced brain size and cognitive disability. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2012]

CENPJ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 13-24892817-T-C is Benign according to our data. Variant chr13-24892817-T-C is described in ClinVar as [Benign]. Clinvar id is 158207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-24892817-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.21 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPJ	NM_018451.5 link	c.3042A>G	p.Glu1014Glu	synonymous_variant	Exon 10 of 17	ENST00000381884.9	NP_060921.3	Q9HC77-1A8K8P1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CENPJ	ENST00000381884.9 link	c.3042A>G	p.Glu1014Glu	synonymous_variant	Exon 10 of 17	1	NM_018451.5	ENSP00000371308.4	Q9HC77-1
CENPJ	ENST00000418179.1 link	c.285A>G	p.Glu95Glu	synonymous_variant	Exon 3 of 4	1		ENSP00000399334.1	H0Y5L8
CENPJ	ENST00000616936.4 link	n.3042A>G		non_coding_transcript_exon_variant	Exon 10 of 16	1		ENSP00000477511.1	Q9HC77-2
CENPJ	ENST00000545981.6 link	n.3042A>G		non_coding_transcript_exon_variant	Exon 10 of 18	2		ENSP00000441090.2	F6VUX8

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73107

AN:

151358

Hom.:

18914

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.580

Gnomad ASJ

AF:

0.508

Gnomad EAS

AF:

0.717

Gnomad SAS

AF:

0.490

Gnomad FIN

AF:

0.632

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.534

Gnomad OTH

AF:

0.485

GnomAD3 exomes

AF:

0.549

AC:

137988

AN:

251456

Hom.:

39117

AF XY:

0.544

AC XY:

73993

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.284

Gnomad AMR exome

AF:

0.649

Gnomad ASJ exome

AF:

0.504

Gnomad EAS exome

AF:

0.712

Gnomad SAS exome

AF:

0.496

Gnomad FIN exome

AF:

0.625

Gnomad NFE exome

AF:

0.534

Gnomad OTH exome

AF:

0.543

GnomAD4 exome

AF:

0.543

AC:

792195

AN:

1459432

Hom.:

217968

Cov.:

AF XY:

0.541

AC XY:

393000

AN XY:

726172

show subpopulations

Gnomad4 AFR exome

AF:

0.285

Gnomad4 AMR exome

AF:

0.639

Gnomad4 ASJ exome

AF:

0.501

Gnomad4 EAS exome

AF:

0.712

Gnomad4 SAS exome

AF:

0.496

Gnomad4 FIN exome

AF:

0.618

Gnomad4 NFE exome

AF:

0.543

Gnomad4 OTH exome

AF:

0.529

GnomAD4 genome

AF:

0.483

AC:

73158

AN:

151476

Hom.:

18933

Cov.:

AF XY:

0.490

AC XY:

36199

AN XY:

73950

show subpopulations

Gnomad4 AFR

AF:

0.297

Gnomad4 AMR

AF:

0.580

Gnomad4 ASJ

AF:

0.508

Gnomad4 EAS

AF:

0.718

Gnomad4 SAS

AF:

0.490

Gnomad4 FIN

AF:

0.632

Gnomad4 NFE

AF:

0.534

Gnomad4 OTH

AF:

0.482

Alfa

AF:

0.508

Hom.:

24821

Bravo

AF:

0.473

Asia WGS

AF:

0.559

AC:

1937

AN:

3476

EpiCase

AF:

0.520

EpiControl

AF:

0.528

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 28, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 20, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

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

- -

Seckel syndrome 4

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Microcephaly 6, primary, autosomal recessive

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 22, 2021

Genome-Nilou Lab

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

-0.53

CADD

Benign

9.0

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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