chr13-24882493-G-GT

Position:

• chr13-24882493-G-GT

Variant summary

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

The NM_018451.5(CENPJ):​c.*683_*684insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9690 hom., cov: 0)
  • Exomes 𝑓: 0.32 (2 hom.)
• Consequence: CENPJ NM_018451.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.09

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 13-24882493-G-GT is Benign according to our data. Variant chr13-24882493-G-GT is described in ClinVar as [Benign]. Clinvar id is 311588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPJ	NM_018451.5	c.*683_*684insA		3_prime_UTR_variant	17/17	ENST00000381884.9	NP_060921.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPJ	ENST00000381884.9	c.*683_*684insA		3_prime_UTR_variant	17/17	1	NM_018451.5	ENSP00000371308	P1
CENPJ	ENST00000616936.4	c.*1354_*1355insA		3_prime_UTR_variant, NMD_transcript_variant	16/16	1		ENSP00000477511

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52232 AN: 151678 Hom.: 9684 Cov.: 0

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.316 AC: 12 AN: 38 Hom.: 2 Cov.: 0 AF XY: 0.278 AC XY: 5 AN XY: 18

Gnomad4 AMR exome AF: 0.167

Gnomad4 NFE exome AF: 0.344

GnomAD4 genome AF: 0.344 AC: 52259 AN: 151788 Hom.: 9690 Cov.: 0 AF XY: 0.350 AC XY: 25952 AN XY: 74180

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.346

Alfa AF: 0.360 Hom.: 1268

Bravo AF: 0.335

Asia WGS AF: 0.368 AC: 1277 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary Microcephaly, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 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

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

Publications

LitVar

Other links and lift over

dbSNP: rs397718122; hg19: chr13-25456631;