rs112133852

Positions:

chr13-24906805-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_018451.5(CENPJ):c.1233G>A(p.Pro411Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000711 in 1,614,166 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00043 ( 5 hom. )

Consequence

CENPJ
NM_018451.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.426

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:

CENPJ (HGNC:):

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=-0.83).

BP6

Variant 13-24906805-C-T is Benign according to our data. Variant chr13-24906805-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 158191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-24906805-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.426 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00341 (519/152278) while in subpopulation AFR AF= 0.0118 (490/41564). AF 95% confidence interval is 0.0109. There are 1 homozygotes in gnomad4. There are 234 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPJ	NM_018451.5 linkuse as main transcript	c.1233G>A	p.Pro411Pro	synonymous_variant	7/17	ENST00000381884.9	NP_060921.3	Q9HC77-1A8K8P1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CENPJ	ENST00000381884.9 linkuse as main transcript	c.1233G>A	p.Pro411Pro	synonymous_variant	7/17	1	NM_018451.5	ENSP00000371308.4	Q9HC77-1
CENPJ	ENST00000616936.4 linkuse as main transcript	n.1233G>A		non_coding_transcript_exon_variant	7/16	1		ENSP00000477511.1	Q9HC77-2
CENPJ	ENST00000545981.6 linkuse as main transcript	n.1233G>A		non_coding_transcript_exon_variant	7/18	2		ENSP00000441090.2	F6VUX8

Frequencies

GnomAD3 genomes

AF:

0.00339

AC:

516

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000959

AC:

241

AN:

251372

Hom.:

AF XY:

0.000780

AC XY:

106

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.0134

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000792

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000430

AC:

628

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000380

AC XY:

276

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0122

Gnomad4 AMR exome

AF:

0.000492

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000115

Gnomad4 OTH exome

AF:

0.000795

GnomAD4 genome

AF:

0.00341

AC:

519

AN:

152278

Hom.:

Cov.:

AF XY:

0.00314

AC XY:

234

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0118

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00166

Hom.:

Bravo

AF:

0.00359

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 26, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 11, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	CENPJ: BP4, BP7, BS1 -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 08, 2013

- -

Seckel syndrome 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

Microcephaly 6, primary, autosomal recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

CENPJ-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 16, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.71

DANN

Benign

0.25

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