13-24882769-CAG-C

Position:

• chr13-24882769-CAG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018451.5(CENPJ):​c.*406_*407del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00557 in 188,686 control chromosomes in the GnomAD database, including 31 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (23 hom., cov: 31)
  • Exomes 𝑓: 0.0066 (8 hom.)
• Consequence: CENPJ NM_018451.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.792

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 -10 ACMG points.

• BP6: Variant 13-24882769-CAG-C is Benign according to our data. Variant chr13-24882769-CAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 311596.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPJ	NM_018451.5	c.*406_*407del		3_prime_UTR_variant	17/17	ENST00000381884.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPJ	ENST00000381884.9	c.*406_*407del		3_prime_UTR_variant	17/17	1	NM_018451.5	P1
CENPJ	ENST00000616936.4	c.*1077_*1078del		3_prime_UTR_variant, NMD_transcript_variant	16/16	1

Frequencies

GnomAD3 genomes AF: 0.00530 AC: 807 AN: 152150 Hom.: 23 Cov.: 31

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.0812

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.00368

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.00814

GnomAD4 exome AF: 0.00665 AC: 242 AN: 36418 Hom.: 8 AF XY: 0.00671 AC XY: 127 AN XY: 18936

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0197

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0941

Gnomad4 SAS exome AF: 0.00291

Gnomad4 FIN exome AF: 0.00562

Gnomad4 NFE exome AF: 0.00103

Gnomad4 OTH exome AF: 0.00746

GnomAD4 genome AF: 0.00531 AC: 809 AN: 152268 Hom.: 23 Cov.: 31 AF XY: 0.00607 AC XY: 452 AN XY: 74450

Gnomad4 AFR AF: 0.000866

Gnomad4 AMR AF: 0.0154

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.0812

Gnomad4 SAS AF: 0.00497

Gnomad4 FIN AF: 0.00368

Gnomad4 NFE AF: 0.000529

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00281 Hom.: 0

Bravo AF: 0.00708

Asia WGS AF: 0.0380 AC: 130 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Primary Microcephaly, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Seckel syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs141666267; hg19: chr13-25456907;