Genetic Variant CPAP:c.*308_*310dupAAG (chr13-24882866-A-ACTT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018451.5(CPAP):c.*308_*310dupAAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000308 in 357,262 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 24)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

CPAP
NM_018451.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.284

Publications

0 publications found

Variant links:

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]

CPAP links:

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]

RNF17 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CPAP	NM_018451.5	MANE Select	c.308_310dupAAG	3_prime_UTR	Exon 17 of 17	NP_060921.3
CPAP	NR_047594.2		n.4609_4611dupAAG	non_coding_transcript_exon	Exon 18 of 18
CPAP	NR_047595.2		n.4407_4409dupAAG	non_coding_transcript_exon	Exon 16 of 16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CPAP	ENST00000381884.9	TSL:1 MANE Select	c.308_310dupAAG	3_prime_UTR	Exon 17 of 17	ENSP00000371308.4	Q9HC77-1
CPAP	ENST00000616936.4	TSL:1	n.979_981dupAAG	non_coding_transcript_exon	Exon 16 of 16	ENSP00000477511.1	Q9HC77-2
CPAP	ENST00000616936.4	TSL:1	n.979_981dupAAG	3_prime_UTR	Exon 16 of 16	ENSP00000477511.1	Q9HC77-2

Frequencies

GnomAD3 genomes

AF:

0.0000207

AC:

AN:

145236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000681

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000303

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000377

AC:

AN:

212026

Hom.:

Cov.:

AF XY:

0.0000434

AC XY:

AN XY:

115224

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

5852

American (AMR)

AF:

0.00

AC:

AN:

8904

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5656

East Asian (EAS)

AF:

0.00

AC:

AN:

9782

South Asian (SAS)

AF:

0.00

AC:

AN:

34948

European-Finnish (FIN)

AF:

0.000103

AC:

AN:

9710

Middle Eastern (MID)

AF:

0.00

AC:

AN:

862

European-Non Finnish (NFE)

AF:

0.0000479

AC:

AN:

125180

Other (OTH)

AF:

0.0000898

AC:

AN:

11132

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000255511), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.362

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000207

AC:

AN:

145236

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70866

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38352

American (AMR)

AF:

0.0000681

AC:

AN:

14690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3286

East Asian (EAS)

AF:

0.00

AC:

AN:

5128

South Asian (SAS)

AF:

0.00

AC:

AN:

4268

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10350

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0000303

AC:

AN:

66034

Other (OTH)

AF:

0.00

AC:

AN:

1978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

385

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.28

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

13-24882866-ACTT-ACTTCTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over