chr13-24892636-T-C

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.3216+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 1,611,198 control chromosomes in the GnomAD database, including 538,374 homozygotes. In-silico tool predicts 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 0.78 ( 46483 hom., cov: 29)

Exomes 𝑓: 0.82 ( 491891 hom. )

Consequence

CENPJ
NM_018451.5 splice_region, intron

Scores

Splicing: ADA: 0.0002216

Clinical Significance

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

Conservation

PhyloP100: -0.975

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 (BayesDel_noAF=-0.9).

BP6

Variant 13-24892636-T-C is Benign according to our data. Variant chr13-24892636-T-C is described in ClinVar as [Benign]. Clinvar id is 158208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-24892636-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPJ	NM_018451.5 link	c.3216+7A>G		splice_region_variant, intron_variant	Intron 10 of 16	ENST00000381884.9	NP_060921.3	Q9HC77-1A8K8P1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CENPJ	ENST00000381884.9 link	c.3216+7A>G	splice_region_variant, intron_variant	Intron 10 of 16	1	NM_018451.5	ENSP00000371308.4	Q9HC77-1
CENPJ	ENST00000418179.1 link	c.459+7A>G	splice_region_variant, intron_variant	Intron 3 of 3	1		ENSP00000399334.1	H0Y5L8
CENPJ	ENST00000616936.4 link	n.3216+7A>G	splice_region_variant, intron_variant	Intron 10 of 15	1		ENSP00000477511.1	Q9HC77-2
CENPJ	ENST00000545981.6 link	n.3216+7A>G	splice_region_variant, intron_variant	Intron 10 of 17	2		ENSP00000441090.2	F6VUX8

Frequencies

GnomAD3 genomes

AF:

0.777

AC:

118044

AN:

151832

Hom.:

46453

Cov.:

show subpopulations

Gnomad AFR

AF:

0.655

Gnomad AMI

AF:

0.791

Gnomad AMR

AF:

0.820

Gnomad ASJ

AF:

0.772

Gnomad EAS

AF:

0.852

Gnomad SAS

AF:

0.666

Gnomad FIN

AF:

0.888

Gnomad MID

AF:

0.722

Gnomad NFE

AF:

0.828

Gnomad OTH

AF:

0.767

GnomAD3 exomes

AF:

0.808

AC:

203202

AN:

251418

Hom.:

82949

AF XY:

0.801

AC XY:

108889

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.646

Gnomad AMR exome

AF:

0.880

Gnomad ASJ exome

AF:

0.762

Gnomad EAS exome

AF:

0.845

Gnomad SAS exome

AF:

0.672

Gnomad FIN exome

AF:

0.893

Gnomad NFE exome

AF:

0.828

Gnomad OTH exome

AF:

0.814

GnomAD4 exome

AF:

0.819

AC:

1195413

AN:

1459248

Hom.:

491891

Cov.:

AF XY:

0.815

AC XY:

591576

AN XY:

726116

show subpopulations

Gnomad4 AFR exome

AF:

0.646

Gnomad4 AMR exome

AF:

0.873

Gnomad4 ASJ exome

AF:

0.761

Gnomad4 EAS exome

AF:

0.864

Gnomad4 SAS exome

AF:

0.677

Gnomad4 FIN exome

AF:

0.893

Gnomad4 NFE exome

AF:

0.831

Gnomad4 OTH exome

AF:

0.798

GnomAD4 genome

AF:

0.777

AC:

118120

AN:

151950

Hom.:

46483

Cov.:

AF XY:

0.778

AC XY:

57782

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.655

Gnomad4 AMR

AF:

0.820

Gnomad4 ASJ

AF:

0.772

Gnomad4 EAS

AF:

0.852

Gnomad4 SAS

AF:

0.665

Gnomad4 FIN

AF:

0.888

Gnomad4 NFE

AF:

0.828

Gnomad4 OTH

AF:

0.759

Alfa

AF:

0.808

Hom.:

31121

Bravo

AF:

0.770

Asia WGS

AF:

0.725

AC:

2520

AN:

3478

EpiCase

AF:

0.813

EpiControl

AF:

0.815

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

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

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

- -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

- -

Apr 09, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:4

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

- -

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

- -

Seckel syndrome 4

Benign:2

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. -

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 12, 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

-0.90

CADD

Benign

0.088

DANN

Benign

0.32

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00022

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.040

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