Variant chr2-219173396-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015680.6(CNPPD1):c.644C>T(p.Pro215Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000564 in 1,613,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

CNPPD1
NM_015680.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.81

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07166934).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNPPD1	NM_015680.6 linkuse as main transcript	c.644C>T	p.Pro215Leu	missense_variant	7/8	ENST00000360507.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CNPPD1	ENST00000360507.10 linkuse as main transcript	c.644C>T	p.Pro215Leu	missense_variant	7/8	1	NM_015680.6	P1
CNPPD1	ENST00000409789.5 linkuse as main transcript	c.644C>T	p.Pro215Leu	missense_variant	8/9	1		P1
CNPPD1	ENST00000453038.5 linkuse as main transcript	c.644C>T	p.Pro215Leu	missense_variant	8/9	2
CNPPD1	ENST00000451647.1 linkuse as main transcript	c.725C>T	p.Pro242Leu	missense_variant	6/7	3

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000639

AC:

AN:

250492

Hom.:

AF XY:

0.0000811

AC XY:

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.0000622

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000973

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000547

AC:

AN:

1461396

Hom.:

Cov.:

AF XY:

0.0000633

AC XY:

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000414

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2021

The c.644C>T (p.P215L) alteration is located in exon 7 (coding exon 7) of the CNPPD1 gene. This alteration results from a C to T substitution at nucleotide position 644, causing the proline (P) at amino acid position 215 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Benign

0.81

DEOGEN2

Benign

0.0011

T;T;.;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.0052

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.89

.;D;D;D

M_CAP

Benign

0.0049

MetaRNN

Benign

0.072

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;N;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.050

N;N;N;N

REVEL

Benign

0.058

Sift

Benign

0.29

T;T;T;T

Sift4G

Benign

0.32

T;T;.;T

Polyphen

0.36

B;B;.;.

Vest4

0.31

MVP

0.33

MPC

0.24

ClinPred

0.028

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.029

gMVP

0.24

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over