Genetic Variant CCNP:p.Pro247Leu (chr19-40223236-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_024877.4(CCNP):c.740C>T(p.Pro247Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,546,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

CCNP
NM_024877.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.02

Publications

0 publications found

Variant links:

Genes affected

CCNP (HGNC:25805): (cyclin P) Predicted to enable cyclin-dependent protein serine/threonine kinase regulator activity. Predicted to be involved in mitotic cell cycle phase transition and regulation of cyclin-dependent protein serine/threonine kinase activity. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CCNP links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.746

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024877.4. 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
	CCNP	NM_024877.4	MANE Select	c.740C>T	p.Pro247Leu	missense	Exon 5 of 5	NP_079153.2	Q9H8S5-1
	CCNP	NM_001411133.1		c.740C>T	p.Pro247Leu	missense	Exon 5 of 6	NP_001398062.1	M0QZM5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCNP	ENST00000430325.7	TSL:2 MANE Select	c.740C>T	p.Pro247Leu	missense	Exon 5 of 5	ENSP00000396755.2	Q9H8S5-1
CCNP	ENST00000599263.6	TSL:5	c.740C>T	p.Pro247Leu	missense	Exon 5 of 6	ENSP00000470643.2	M0QZM5
CCNP	ENST00000921917.1		c.650C>T	p.Pro217Leu	missense	Exon 4 of 4	ENSP00000591976.1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000477

AC:

AN:

146704

AF XY:

0.0000509

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000661

Gnomad NFE exome

AF:

0.0000905

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000130

AC:

181

AN:

1394386

Hom.:

Cov.:

AF XY:

0.0000990

AC XY:

AN XY:

687094

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31388

American (AMR)

AF:

0.00

AC:

AN:

35146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25054

East Asian (EAS)

AF:

0.00

AC:

AN:

35592

South Asian (SAS)

AF:

0.0000253

AC:

AN:

79014

European-Finnish (FIN)

AF:

0.000144

AC:

AN:

48608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.000148

AC:

159

AN:

1076134

Other (OTH)

AF:

0.000225

AC:

AN:

57766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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

AF:

0.0000657

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.000131

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

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:

0.000121

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000350

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.70

M_CAP

Benign

0.039

MetaRNN

Pathogenic

0.75

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

3.3

PhyloP100

3.0

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-8.6

REVEL

Uncertain

0.31

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Vest4

0.48

MVP

0.64

MPC

1.7

ClinPred

0.97

GERP RS

4.0

Varity_R

0.30

gMVP

0.82

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over