13-24882874-GT-G

Variant summary

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

The NM_018451.5(CENPJ):c.*302del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 359,940 control chromosomes in the GnomAD database, including 7,206 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3187 hom., cov: 27)
  • Exomes 𝑓: 0.19 (4019 hom.)
• Consequence: CENPJ NM_018451.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.897

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 13-24882874-GT-G is Benign according to our data. Variant chr13-24882874-GT-G is described in ClinVar as [Benign]. Clinvar id is 311601.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPJ	NM_018451.5	c.*302del		3_prime_UTR_variant	17/17	ENST00000381884.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPJ	ENST00000381884.9	c.*302del		3_prime_UTR_variant	17/17	1	NM_018451.5	P1
CENPJ	ENST00000616936.4	c.*973del		3_prime_UTR_variant, NMD_transcript_variant	16/16	1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 29749 AN: 150270 Hom.: 3175 Cov.: 27

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0940

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.279

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.186 AC: 38971 AN: 209548 Hom.: 4019 Cov.: 0 AF XY: 0.196 AC XY: 22234 AN XY: 113504

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.235

Gnomad4 EAS exome AF: 0.0921

Gnomad4 SAS exome AF: 0.303

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.166

Gnomad4 OTH exome AF: 0.186

GnomAD4 genome AF: 0.198 AC: 29778 AN: 150392 Hom.: 3187 Cov.: 27 AF XY: 0.198 AC XY: 14559 AN XY: 73432

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.0936

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.223

Bravo AF: 0.200

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Primary Microcephaly, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs138938177; hg19: chr13-25457012;