rs17402892

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018451.5(CENPJ):c.2635T>G(p.Ser879Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,613,748 control chromosomes in the GnomAD database, including 14,414 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 908 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13506 hom. )

Consequence

CENPJ
NM_018451.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10O:1

Conservation

PhyloP100: -0.371

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011765659).

BP6

Variant 13-24905403-A-C is Benign according to our data. Variant chr13-24905403-A-C is described in ClinVar as [Benign]. Clinvar id is 21661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-24905403-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPJ	NM_018451.5 link	c.2635T>G	p.Ser879Ala	missense_variant	Exon 7 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.2635T>G	p.Ser879Ala	missense_variant	Exon 7 of 17	1	NM_018451.5	ENSP00000371308.4	Q9HC77-1
CENPJ	ENST00000616936.4 link	n.2635T>G		non_coding_transcript_exon_variant	Exon 7 of 16	1		ENSP00000477511.1	Q9HC77-2
CENPJ	ENST00000545981.6 link	n.2635T>G		non_coding_transcript_exon_variant	Exon 7 of 18	2		ENSP00000441090.2	F6VUX8

Frequencies

GnomAD3 genomes

AF:

0.0998

AC:

15176

AN:

152066

Hom.:

909

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0366

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.0918

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.0752

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.101

GnomAD3 exomes

AF:

0.110

AC:

27671

AN:

251310

Hom.:

1775

AF XY:

0.112

AC XY:

15166

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.0351

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.118

Gnomad EAS exome

AF:

0.000489

Gnomad SAS exome

AF:

0.0801

Gnomad FIN exome

AF:

0.132

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.131

AC:

191425

AN:

1461564

Hom.:

13506

Cov.:

AF XY:

0.130

AC XY:

94185

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.0310

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.123

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.0825

Gnomad4 FIN exome

AF:

0.133

Gnomad4 NFE exome

AF:

0.144

Gnomad4 OTH exome

AF:

0.117

GnomAD4 genome

AF:

0.0997

AC:

15169

AN:

152184

Hom.:

908

Cov.:

AF XY:

0.0976

AC XY:

7265

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0365

Gnomad4 AMR

AF:

0.0915

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.00367

Gnomad4 SAS

AF:

0.0748

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.143

Gnomad4 OTH

AF:

0.0995

Alfa

AF:

0.129

Hom.:

2192

Bravo

AF:

0.0950

TwinsUK

AF:

0.148

AC:

547

ALSPAC

AF:

0.148

AC:

572

ESP6500AA

AF:

0.0418

AC:

184

ESP6500EA

AF:

0.138

AC:

1189

ExAC

AF:

0.109

AC:

13276

Asia WGS

AF:

0.0450

AC:

157

AN:

3478

EpiCase

AF:

0.140

EpiControl

AF:

0.141

ClinVar

Significance: Benign

Submissions summary: Benign:10Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

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

- -

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

Significance: Benign

Review Status: no assertion criteria provided

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

- -

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Apr 20, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Microcephaly 6, primary, autosomal recessive

Benign:1Other:1

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Jan 12, 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. -

Seckel syndrome 4

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

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

0.067

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.59

CADD

Benign

1.4

DANN

Benign

0.96

DEOGEN2

Benign

0.0058

.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.39

T;T;T

MetaRNN

Benign

0.0012

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.65

.;N;N

REVEL

Benign

0.073

Sift

Benign

0.21

.;T;T

Sift4G

Benign

0.72

T;T;T

Polyphen

0.0030

.;B;.

Vest4

0.032

MPC

0.10

ClinPred

0.00072

GERP RS

-0.95

Varity_R

0.031

gMVP

0.047

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