Variant 2-219173034-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015680.6(CNPPD1):c.785T>C(p.Ile262Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,612,714 control chromosomes in the GnomAD database, including 276,417 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.50 ( 20253 hom., cov: 31)

Exomes 𝑓: 0.59 ( 256164 hom. )

Consequence

CNPPD1
NM_015680.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.240

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.320183E-5).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNPPD1	NM_015680.6 linkuse as main transcript	c.785T>C	p.Ile262Thr	missense_variant	8/8	ENST00000360507.10	NP_056495.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CNPPD1	ENST00000360507.10 linkuse as main transcript	c.785T>C	p.Ile262Thr	missense_variant	8/8	1	NM_015680.6	ENSP00000353698	P1
CNPPD1	ENST00000409789.5 linkuse as main transcript	c.785T>C	p.Ile262Thr	missense_variant	9/9	1		ENSP00000386277	P1
CNPPD1	ENST00000453038.5 linkuse as main transcript	c.785T>C	p.Ile262Thr	missense_variant	9/9	2		ENSP00000410109
CNPPD1	ENST00000451647.1 linkuse as main transcript			downstream_gene_variant		3		ENSP00000405997

Frequencies

GnomAD3 genomes

AF:

0.497

AC:

75507

AN:

151794

Hom.:

20256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.306

Gnomad AMI

AF:

0.587

Gnomad AMR

AF:

0.445

Gnomad ASJ

AF:

0.612

Gnomad EAS

AF:

0.258

Gnomad SAS

AF:

0.576

Gnomad FIN

AF:

0.619

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.612

Gnomad OTH

AF:

0.503

GnomAD3 exomes

AF:

0.533

AC:

132948

AN:

249246

Hom.:

37467

AF XY:

0.549

AC XY:

74006

AN XY:

134860

show subpopulations

Gnomad AFR exome

AF:

0.301

Gnomad AMR exome

AF:

0.389

Gnomad ASJ exome

AF:

0.613

Gnomad EAS exome

AF:

0.272

Gnomad SAS exome

AF:

0.594

Gnomad FIN exome

AF:

0.627

Gnomad NFE exome

AF:

0.612

Gnomad OTH exome

AF:

0.547

GnomAD4 exome

AF:

0.586

AC:

856021

AN:

1460802

Hom.:

256164

Cov.:

AF XY:

0.588

AC XY:

426963

AN XY:

726654

show subpopulations

Gnomad4 AFR exome

AF:

0.291

Gnomad4 AMR exome

AF:

0.395

Gnomad4 ASJ exome

AF:

0.623

Gnomad4 EAS exome

AF:

0.266

Gnomad4 SAS exome

AF:

0.595

Gnomad4 FIN exome

AF:

0.622

Gnomad4 NFE exome

AF:

0.612

Gnomad4 OTH exome

AF:

0.560

GnomAD4 genome

AF:

0.497

AC:

75529

AN:

151912

Hom.:

20253

Cov.:

AF XY:

0.499

AC XY:

37034

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.305

Gnomad4 AMR

AF:

0.446

Gnomad4 ASJ

AF:

0.612

Gnomad4 EAS

AF:

0.259

Gnomad4 SAS

AF:

0.576

Gnomad4 FIN

AF:

0.619

Gnomad4 NFE

AF:

0.612

Gnomad4 OTH

AF:

0.497

Alfa

AF:

0.584

Hom.:

59311

Bravo

AF:

0.471

TwinsUK

AF:

0.607

AC:

2251

ALSPAC

AF:

0.610

AC:

2352

ESP6500AA

AF:

0.311

AC:

1370

ESP6500EA

AF:

0.609

AC:

5239

ExAC

AF:

0.540

AC:

65508

Asia WGS

AF:

0.344

AC:

1198

AN:

3478

EpiCase

AF:

0.606

EpiControl

AF:

0.607

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

9.4

DANN

Benign

0.52

DEOGEN2

Benign

0.00076

T;T;.

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.12

.;T;T

MetaRNN

Benign

0.000013

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.20

N;N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.29

PROVEAN

Benign

0.75

N;N;N

REVEL

Benign

0.024

Sift

Benign

0.62

T;T;T

Sift4G

Benign

0.68

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.0070

MPC

0.29

ClinPred

0.00050

GERP RS

2.2

Varity_R

0.018

gMVP

0.12

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over