13-24912773-G-T

Position:

chr13-24912773-G-T

Variant summary

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

The NM_018451.5(CENPJ):c.253C>A(p.Pro85Thr) 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 1,613,882 control chromosomes in the GnomAD database, including 14,400 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 906 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13494 hom. )

Consequence

CENPJ
NM_018451.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 1.39

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=0.0021811724).

BP6

Variant 13-24912773-G-T is Benign according to our data. Variant chr13-24912773-G-T is described in ClinVar as [Benign]. Clinvar id is 158203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-24912773-G-T 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/exons	MANE	Protein	UniProt
CENPJ	NM_018451.5 linkuse as main transcript	c.253C>A	p.Pro85Thr	missense_variant	2/17	ENST00000381884.9	NP_060921.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPJ	ENST00000381884.9 linkuse as main transcript	c.253C>A	p.Pro85Thr	missense_variant	2/17	1	NM_018451.5	ENSP00000371308	P1	Q9HC77-1
CENPJ	ENST00000616936.4 linkuse as main transcript	c.253C>A	p.Pro85Thr	missense_variant, NMD_transcript_variant	2/16	1		ENSP00000477511		Q9HC77-2
CENPJ	ENST00000545981.6 linkuse as main transcript	c.253C>A	p.Pro85Thr	missense_variant, NMD_transcript_variant	2/18	2		ENSP00000441090

Frequencies

GnomAD3 genomes

AF:

0.0997

AC:

15157

AN:

151992

Hom.:

907

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0364

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.0917

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.00365

Gnomad SAS

AF:

0.0754

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.0828

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.100

GnomAD3 exomes

AF:

0.110

AC:

27651

AN:

251474

Hom.:

1769

AF XY:

0.112

AC XY:

15155

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.0346

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:

0.131

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.131

AC:

191389

AN:

1461772

Hom.:

13494

Cov.:

AF XY:

0.130

AC XY:

94171

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.0304

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:

0.0996

AC:

15150

AN:

152110

Hom.:

906

Cov.:

AF XY:

0.0975

AC XY:

7245

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0363

Gnomad4 AMR

AF:

0.0915

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.00366

Gnomad4 SAS

AF:

0.0751

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.143

Gnomad4 OTH

AF:

0.0989

Alfa

AF:

0.129

Hom.:

3035

Bravo

AF:

0.0947

TwinsUK

AF:

0.147

AC:

546

ALSPAC

AF:

0.148

AC:

570

ESP6500AA

AF:

0.0409

AC:

180

ESP6500EA

AF:

0.138

AC:

1186

ExAC

AF:

0.109

AC:

13260

Asia WGS

AF:

0.0450

AC:

158

AN:

3478

EpiCase

AF:

0.140

EpiControl

AF:

0.141

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 08, 2014	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -

Seckel syndrome 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.68

CADD

Benign

8.2

DANN

Benign

0.84

DEOGEN2

Benign

0.011

.;T;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.71

T;T;T

MetaRNN

Benign

0.0022

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-2.5

.;N;D

REVEL

Benign

0.045

Sift

Benign

0.066

.;T;T

Sift4G

Benign

0.12

T;T;T

Polyphen

0.046

.;B;.

Vest4

0.033

MPC

0.15

ClinPred

0.0037

GERP RS

2.4

Varity_R

0.040

gMVP

0.16

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