Genetic Variant CPAP:p.Gln1150Glu (chr13-24885305-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000381884.9(CENPJ):c.3448C>G(p.Gln1150Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q1150Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CENPJ
ENST00000381884.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.768

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09085703).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000381884.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CPAP	NM_018451.5	MANE Select	c.3448C>G	p.Gln1150Glu	missense	Exon 13 of 17	NP_060921.3
CPAP	NR_047594.2		n.3732C>G		non_coding_transcript_exon	Exon 14 of 18
CPAP	NR_047595.2		n.3530C>G		non_coding_transcript_exon	Exon 12 of 16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CENPJ	ENST00000381884.9	TSL:1 MANE Select	c.3448C>G	p.Gln1150Glu	missense	Exon 13 of 17	ENSP00000371308.4
CENPJ	ENST00000616936.4	TSL:1	n.*102C>G		non_coding_transcript_exon	Exon 12 of 16	ENSP00000477511.1
CENPJ	ENST00000616936.4	TSL:1	n.*102C>G		3_prime_UTR	Exon 12 of 16	ENSP00000477511.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460294

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726594

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110572

Other (OTH)

AF:

0.00

AC:

AN:

60342

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

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00000404

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.0049

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.38

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.61

M_CAP

Benign

0.0060

MetaRNN

Benign

0.091

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

0.77

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.74

REVEL

Benign

0.045

Sift

Benign

0.21

Sift4G

Benign

0.41

Polyphen

0.0010

Vest4

0.12

MutPred

0.23

Gain of catalytic residue at I1153 (P = 0.0161)

MVP

0.41

MPC

0.13

ClinPred

0.14

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.40

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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.

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