Variant chr13-24907147-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_018451.5(CENPJ):c.1021T>C(p.Tyr341His) variant causes a missense change. The variant allele was found at a frequency of 0.00000656 in 152,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

CENPJ
NM_018451.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.76

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1

In a mutagenesis_site Decreases interaction with alpha/beta-tubulin; when associated with A-338 and A-339. (size 0) in uniprot entity CENPJ_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32180095).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPJ	NM_018451.5 linkuse as main transcript	c.1021T>C	p.Tyr341His	missense_variant	6/17	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.1021T>C	p.Tyr341His	missense_variant	6/17	1	NM_018451.5	ENSP00000371308.4	Q9HC77-1
CENPJ	ENST00000616936.4 linkuse as main transcript	n.1021T>C		non_coding_transcript_exon_variant	6/16	1		ENSP00000477511.1	Q9HC77-2
CENPJ	ENST00000545981.6 linkuse as main transcript	n.1021T>C		non_coding_transcript_exon_variant	6/18	2		ENSP00000441090.2	F6VUX8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

.;T;T

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

M;M;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-2.0

.;N;D

REVEL

Benign

0.12

Sift

Pathogenic

0.0

.;D;D

Sift4G

Benign

0.13

T;D;T

Polyphen

0.99

.;D;.

Vest4

0.55

MutPred

0.29

Gain of catalytic residue at I346 (P = 0.0196);Gain of catalytic residue at I346 (P = 0.0196);Gain of catalytic residue at I346 (P = 0.0196);

MVP

0.71

MPC

0.61

ClinPred

0.93

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.29

gMVP

0.35

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over