Variant chr13-24882581-C-CAT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_018451.5(CENPJ):c.*595_*596insAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00637 in 153,598 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0064 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0052 ( 0 hom. )

Consequence

CENPJ
NM_018451.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: 0.127

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:

RNF17 (HGNC:):

RNF17 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 13-24882581-C-CAT is Benign according to our data. Variant chr13-24882581-C-CAT is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 311590.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=2}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00638 (972/152242) while in subpopulation NFE AF= 0.00994 (676/68016). AF 95% confidence interval is 0.00932. There are 4 homozygotes in gnomad4. There are 470 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPJ	NM_018451.5 linkuse as main transcript	c.595_596insAT		3_prime_UTR_variant	17/17	ENST00000381884.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPJ	ENST00000381884.9 linkuse as main transcript	c.595_596insAT		3_prime_UTR_variant	17/17	1	NM_018451.5	P1	Q9HC77-1
CENPJ	ENST00000616936.4 linkuse as main transcript	c.1266_1267insAT		3_prime_UTR_variant, NMD_transcript_variant	16/16	1			Q9HC77-2

Frequencies

GnomAD3 genomes

AF:

0.00639

AC:

972

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00215

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000832

Gnomad FIN

AF:

0.00914

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00992

Gnomad OTH

AF:

0.00526

GnomAD4 exome

AF:

0.00516

AC:

AN:

1356

Hom.:

Cov.:

AF XY:

0.00404

AC XY:

AN XY:

742

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00649

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:

0.00499

Gnomad4 OTH exome

AF:

0.0200

GnomAD4 genome

AF:

0.00638

AC:

972

AN:

152242

Hom.:

Cov.:

AF XY:

0.00631

AC XY:

470

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00214

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000833

Gnomad4 FIN

AF:

0.00914

Gnomad4 NFE

AF:

0.00994

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00783

Hom.:

Bravo

AF:

0.00558

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 22, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2023	CENPJ: BS2 -

Primary Microcephaly, Recessive

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Seckel syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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