Genetic Variant NM_015680.6:c.971C>G (chr2-219172848-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 NM_015680.6(CNPPD1):c.971C>G(p.Pro324Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000585 in 1,588,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

CNPPD1
NM_015680.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.21

Publications

0 publications found

Variant links:

Genes affected

CNPPD1 (HGNC:25220): (cyclin Pas1/PHO80 domain containing 1) Predicted to enable cyclin-dependent protein serine/threonine kinase regulator activity. Predicted to be involved in regulation of cyclin-dependent protein serine/threonine kinase activity. Predicted to be integral component of membrane. Predicted to be part of cyclin-dependent protein kinase holoenzyme complex. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CNPPD1 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=0.12090206).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015680.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNPPD1	NM_015680.6	MANE Select	c.971C>G	p.Pro324Arg	missense	Exon 8 of 8	NP_056495.4
CNPPD1	NM_001321389.2		c.971C>G	p.Pro324Arg	missense	Exon 9 of 9	NP_001308318.2	Q9BV87
CNPPD1	NM_001321390.2		c.971C>G	p.Pro324Arg	missense	Exon 9 of 9	NP_001308319.2	Q9BV87

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNPPD1	ENST00000360507.10	TSL:1 MANE Select	c.971C>G	p.Pro324Arg	missense	Exon 8 of 8	ENSP00000353698.5	Q9BV87
CNPPD1	ENST00000409789.5	TSL:1	c.971C>G	p.Pro324Arg	missense	Exon 9 of 9	ENSP00000386277.1	Q9BV87
CNPPD1	ENST00000874465.1		c.1052C>G	p.Pro351Arg	missense	Exon 8 of 8	ENSP00000544524.1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000567

AC:

AN:

229086

AF XY:

0.0000570

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000388

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000962

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000599

AC:

AN:

1436438

Hom.:

Cov.:

AF XY:

0.0000520

AC XY:

AN XY:

711428

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32972

American (AMR)

AF:

0.00

AC:

AN:

42612

Ashkenazi Jewish (ASJ)

AF:

0.000374

AC:

AN:

24078

East Asian (EAS)

AF:

0.00

AC:

AN:

39504

South Asian (SAS)

AF:

0.00

AC:

AN:

81812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52070

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5550

European-Non Finnish (NFE)

AF:

0.0000683

AC:

AN:

1098568

Other (OTH)

AF:

0.0000337

AC:

AN:

59272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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:

0.0000460

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41434

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.000157

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

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

Benign

0.086

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0049

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.74

M_CAP

Benign

0.0042

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

PhyloP100

3.2

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.55

REVEL

Benign

0.065

Sift

Benign

0.19

Sift4G

Benign

0.62

Polyphen

0.92

Vest4

0.34

MVP

0.44

MPC

0.79

ClinPred

0.15

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.046

gMVP

0.27

Mutation Taster

=80/20

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