rs34991318

chr13-24884094-AGTT-Achr13-24884094-AGTT-AGTTGTT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_018451.5(CENPJ):c.3704-14_3704-12del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,611,820 control chromosomes in the GnomAD database, including 243,098 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19947 hom., cov: 0)
  • Exomes 𝑓: 0.55 (223151 hom.)
• Consequence: CENPJ NM_018451.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 2.18

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]

RNF17 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 13-24884094-AGTT-A is Benign according to our data. Variant chr13-24884094-AGTT-A is described in ClinVar as [Benign]. Clinvar id is 158213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-24884094-AGTT-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPJ	NM_018451.5	c.3704-14_3704-12del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000381884.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPJ	ENST00000381884.9	c.3704-14_3704-12del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_018451.5	P1
CENPJ	ENST00000616936.4	c.*358-14_*358-12del		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		1
CENPJ	ENST00000545981.6	c.*444-14_*444-12del		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75604 AN: 151688 Hom.: 19923 Cov.: 0

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.504

GnomAD3 exomes AF: 0.562 AC: 139681 AN: 248620 Hom.: 40924 AF XY: 0.555 AC XY: 74644 AN XY: 134470

Gnomad AFR exome AF: 0.323

Gnomad AMR exome AF: 0.679

Gnomad ASJ exome AF: 0.505

Gnomad EAS exome AF: 0.799

Gnomad SAS exome AF: 0.497

Gnomad FIN exome AF: 0.630

Gnomad NFE exome AF: 0.532

Gnomad OTH exome AF: 0.550

GnomAD4 exome AF: 0.548 AC: 800492 AN: 1460016 Hom.: 223151 AF XY: 0.546 AC XY: 396853 AN XY: 726442

Gnomad4 AFR exome AF: 0.324

Gnomad4 AMR exome AF: 0.668

Gnomad4 ASJ exome AF: 0.501

Gnomad4 EAS exome AF: 0.816

Gnomad4 SAS exome AF: 0.499

Gnomad4 FIN exome AF: 0.624

Gnomad4 NFE exome AF: 0.543

Gnomad4 OTH exome AF: 0.537

GnomAD4 genome AF: 0.498 AC: 75657 AN: 151804 Hom.: 19947 Cov.: 0 AF XY: 0.505 AC XY: 37497 AN XY: 74178

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.500

Alfa AF: 0.443 Hom.: 2287

Bravo AF: 0.493

Asia WGS AF: 0.598 AC: 2074 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

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	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 17, 2014	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 01, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Seckel syndrome 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Primary Microcephaly, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Microcephaly 6, primary, autosomal recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Seckel syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs34991318; hg19: chr13-25458232;