13-24882866-ACTT-A

Position:

• chr13-24882866-ACTT-A

Variant summary

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

The NM_018451.5(CENPJ):​c.*308_*310delAAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 356,646 control chromosomes in the GnomAD database, including 11,291 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4108 hom., cov: 23)
  • Exomes 𝑓: 0.25 (7183 hom.)
• Consequence: CENPJ NM_018451.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.254

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:10060): (ring finger protein 17) This gene is similar to a mouse gene that encodes a testis-specific protein containing a RING finger domain. Alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 13-24882866-ACTT-A is Benign according to our data. Variant chr13-24882866-ACTT-A is described in ClinVar as [Benign]. Clinvar id is 311599.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPJ	NM_018451.5	c.*308_*310delAAG		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	c.*308_*310delAAG		3_prime_UTR_variant	17/17	1	NM_018451.5	ENSP00000371308.4
CENPJ	ENST00000616936.4	n.*979_*981delAAG		non_coding_transcript_exon_variant	16/16	1		ENSP00000477511.1
CENPJ	ENST00000616936.4	n.*979_*981delAAG		3_prime_UTR_variant	16/16	1		ENSP00000477511.1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 33369 AN: 145168 Hom.: 4111 Cov.: 23

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.0540

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.248 AC: 52454 AN: 211384 Hom.: 7183 AF XY: 0.242 AC XY: 27856 AN XY: 114896

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.257

Gnomad4 EAS exome AF: 0.0479

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.267

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.230 AC: 33351 AN: 145262 Hom.: 4108 Cov.: 23 AF XY: 0.226 AC XY: 15999 AN XY: 70942

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.0536

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.234

Alfa AF: 0.164 Hom.: 385

Bravo AF: 0.212

Asia WGS AF: 0.113 AC: 395 AN: 3478

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: rs796638364; hg19: chr13-25457004;