Variant 16-12665074-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BP4

The NM_018340.3(CPPED1):c.757G>A(p.Gly253Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000648 in 1,606,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.000064 ( 0 hom. )

Consequence

CPPED1
NM_018340.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.97

Variant links:

Genes affected

CPPED1 (HGNC:25632): (calcineurin like phosphoesterase domain containing 1) Predicted to enable metal ion binding activity; protein serine phosphatase activity; and protein threonine phosphatase activity. Predicted to be involved in protein dephosphorylation. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CPPED1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Multiple lines of computational evidence support a deleterious effect 8: BayesDel_addAF, BayesDel_noAF, Cadd, Dann, Eigen, MutationAssessor, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.32048285).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPPED1	NM_018340.3 linkuse as main transcript	c.757G>A	p.Gly253Arg	missense_variant	4/4	ENST00000381774.9	NP_060810.2
CPPED1	NM_001099455.2 linkuse as main transcript	c.331G>A	p.Gly111Arg	missense_variant	3/3		NP_001092925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPPED1	ENST00000381774.9 linkuse as main transcript	c.757G>A	p.Gly253Arg	missense_variant	4/4	1	NM_018340.3	ENSP00000371193	P1	Q9BRF8-1
CPPED1	ENST00000433677.6 linkuse as main transcript	c.331G>A	p.Gly111Arg	missense_variant	3/3	1		ENSP00000411127		Q9BRF8-2
CPPED1	ENST00000261660.4 linkuse as main transcript	c.290-54G>A		intron_variant		2		ENSP00000261660		Q9BRF8-3

Frequencies

GnomAD3 genomes

AF:

0.0000724

AC:

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

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:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000145

AC:

AN:

241054

Hom.:

AF XY:

0.000144

AC XY:

AN XY:

131524

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000584

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00122

Gnomad NFE exome

AF:

0.0000631

Gnomad OTH exome

AF:

0.000173

GnomAD4 exome

AF:

0.0000640

AC:

AN:

1454022

Hom.:

Cov.:

AF XY:

0.0000663

AC XY:

AN XY:

723760

show subpopulations

Gnomad4 AFR exome

AF:

0.0000306

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.00109

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.0000834

GnomAD4 genome

AF:

0.0000724

AC:

AN:

151980

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.0000967

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000347

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

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

Feb 27, 2024

The c.757G>A (p.G253R) alteration is located in exon 4 (coding exon 4) of the CPPED1 gene. This alteration results from a G to A substitution at nucleotide position 757, causing the glycine (G) at amino acid position 253 to be replaced by an arginine (R). 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

Uncertain

0.37

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.45

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.026

T;.

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

D;D

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.32

T;T

MetaSVM

Uncertain

0.75

MutationAssessor

Pathogenic

3.0

M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-5.4

D;D

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0060

D;T

Sift4G

Uncertain

0.026

D;D

Polyphen

1.0

D;D

Vest4

0.45

MutPred

0.50

Gain of solvent accessibility (P = 0.0014);.;

MVP

0.62

MPC

0.071

ClinPred

0.55

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.73

gMVP

0.47

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