NM_018451.5:c.*594_*595dupAT

Variant names:

• chr13-24882581-C-CAT
• rs570468323
• NM_018451.5:c.*594_*595dupAT

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_018451.5(CPAP):​c.*594_*595dupAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00637 in 153,598 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0064 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0052 (0 hom.)
• Consequence: CPAP NM_018451.5 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:2
• Conservation: PhyloP100: 0.127
• 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: Benign. The variant received -9 ACMG points.

• BP6: Variant 13-24882581-C-CAT is Benign according to our data. Variant chr13-24882581-C-CAT is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 311590.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00638 (972/152242) while in subpopulation NFE AF = 0.00994 (676/68016). AF 95% confidence interval is 0.00932. There are 4 homozygotes in GnomAd4. There are 470 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPAP	NM_018451.5	MANE Select	c.*594_*595dupAT		3_prime_UTR	Exon 17 of 17	NP_060921.3
	CPAP	NR_047594.2		n.4895_4896dupAT		non_coding_transcript_exon	Exon 18 of 18
	CPAP	NR_047595.2		n.4693_4694dupAT		non_coding_transcript_exon	Exon 16 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPAP	ENST00000381884.9	TSL:1 MANE Select	c.*594_*595dupAT		3_prime_UTR	Exon 17 of 17	ENSP00000371308.4	Q9HC77-1
	CPAP	ENST00000616936.4	TSL:1	n.*1265_*1266dupAT		non_coding_transcript_exon	Exon 16 of 16	ENSP00000477511.1	Q9HC77-2
	CPAP	ENST00000616936.4	TSL:1	n.*1265_*1266dupAT		3_prime_UTR	Exon 16 of 16	ENSP00000477511.1	Q9HC77-2

Frequencies

GnomAD3 genomes AF: 0.00639 AC: 972 AN: 152126 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.00215

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000832

Gnomad FIN AF: 0.00914

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00992

Gnomad OTH AF: 0.00526

GnomAD4 exome AF: 0.00516 AC: 7 AN: 1356 Hom.: 0 Cov.: 0 AF XY: 0.00404 AC XY: 3 AN XY: 742

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AF: 0.00649 AC: 1 AN: 154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AF: 0.00 AC: 0 AN: 30

South Asian (SAS) AF: 0.00 AC: 0 AN: 86

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00499 AC: 5 AN: 1002

Other (OTH) AF: 0.0200 AC: 1 AN: 50

GnomAD4 genome AF: 0.00638 AC: 972 AN: 152242 Hom.: 4 Cov.: 31 AF XY: 0.00631 AC XY: 470 AN XY: 74432

African (AFR) AF: 0.00214 AC: 89 AN: 41560

American (AMR) AF: 0.00288 AC: 44 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000833 AC: 4 AN: 4804

European-Finnish (FIN) AF: 0.00914 AC: 97 AN: 10608

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00994 AC: 676 AN: 68016

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00783 Hom.: 1

Bravo AF: 0.00558

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	1	-	Primary Microcephaly, Recessive (1)
-	1	-	Seckel syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.13

Splicing

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

Other links and lift over

dbSNP: rs570468323; hg19: chr13-25456719;