Variant rs41306029 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018451.5(CENPJ):c.2678A>C(p.Gln893Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CENPJ
NM_018451.5 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 2.91

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20587704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPJ	NM_018451.5 linkuse as main transcript	c.2678A>C	p.Gln893Pro	missense_variant	7/17	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.2678A>C	p.Gln893Pro	missense_variant	7/17	1	NM_018451.5	ENSP00000371308	P1	Q9HC77-1
CENPJ	ENST00000616936.4 linkuse as main transcript	c.2678A>C	p.Gln893Pro	missense_variant, NMD_transcript_variant	7/16	1		ENSP00000477511		Q9HC77-2
CENPJ	ENST00000545981.6 linkuse as main transcript	c.2678A>C	p.Gln893Pro	missense_variant, NMD_transcript_variant	7/18	2		ENSP00000441090

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461796

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

Microcephaly 6, primary, autosomal recessive

Other:1

not provided, no classification provided

literature only

GeneReviews

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.048

.;T;T

Eigen

Benign

0.029

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.043

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-0.46

MutationAssessor

Uncertain

2.4

M;M;.

MutationTaster

Benign

0.88

D;D

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.2

.;N;D

REVEL

Benign

0.29

Sift

Uncertain

0.0010

.;D;D

Sift4G

Uncertain

0.027

D;D;D

Polyphen

0.076

.;B;.

Vest4

0.17

MutPred

0.28

Gain of catalytic residue at P896 (P = 2e-04);Gain of catalytic residue at P896 (P = 2e-04);Gain of catalytic residue at P896 (P = 2e-04);

MVP

0.82

MPC

0.15

ClinPred

0.89

GERP RS

4.7

Varity_R

0.22

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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