13-24884443-A-ATTCTT

Variant names:

• chr13-24884443-A-ATTCTT
• rs776528706
• NM_018451.5:c.3493_3497dupAAGAA

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_018451.5(CPAP):​c.3493_3497dupAAGAA​(p.Asn1166LysfsTer18) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPAP NM_018451.5 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• Publications: 0 publications found

Genes affected

CPAP (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

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018451.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPAP	NM_018451.5	MANE Select	c.3493_3497dupAAGAA	p.Asn1166LysfsTer18	frameshift	Exon 14 of 17	NP_060921.3
	CPAP	NR_047594.2		n.3777_3781dupAAGAA		non_coding_transcript_exon	Exon 15 of 18
	CPAP	NR_047595.2		n.3575_3579dupAAGAA		non_coding_transcript_exon	Exon 13 of 16

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPJ	ENST00000381884.9	TSL:1 MANE Select	c.3493_3497dupAAGAA	p.Asn1166LysfsTer18	frameshift	Exon 14 of 17	ENSP00000371308.4
	CENPJ	ENST00000616936.4	TSL:1	n.*147_*151dupAAGAA		non_coding_transcript_exon	Exon 13 of 16	ENSP00000477511.1
	CENPJ	ENST00000616936.4	TSL:1	n.*147_*151dupAAGAA		3_prime_UTR	Exon 13 of 16	ENSP00000477511.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4

Splicing

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

Other links and lift over

dbSNP: rs776528706; hg19: chr13-25458581;