Variant 16-12664959-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018340.3(CPPED1):c.872G>A(p.Arg291Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,611,300 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

CPPED1
NM_018340.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.21

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037573963).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPPED1	NM_018340.3 linkuse as main transcript	c.872G>A	p.Arg291Gln	missense_variant	4/4	ENST00000381774.9	NP_060810.2
CPPED1	NM_001099455.2 linkuse as main transcript	c.446G>A	p.Arg149Gln	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.872G>A	p.Arg291Gln	missense_variant	4/4	1	NM_018340.3	ENSP00000371193	P1	Q9BRF8-1
CPPED1	ENST00000433677.6 linkuse as main transcript	c.446G>A	p.Arg149Gln	missense_variant	3/3	1		ENSP00000411127		Q9BRF8-2
CPPED1	ENST00000261660.4 linkuse as main transcript	c.351G>A	p.Pro117=	synonymous_variant	3/3	2		ENSP00000261660		Q9BRF8-3

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000849

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000264

AC:

AN:

246222

Hom.:

AF XY:

0.000261

AC XY:

AN XY:

133870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000568

Gnomad SAS exome

AF:

0.0000660

Gnomad FIN exome

AF:

0.000465

Gnomad NFE exome

AF:

0.000418

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.000150

AC:

219

AN:

1459050

Hom.:

Cov.:

AF XY:

0.000156

AC XY:

113

AN XY:

725984

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000457

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000465

Gnomad4 FIN exome

AF:

0.000599

Gnomad4 NFE exome

AF:

0.000153

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.000171

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000849

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000218

Hom.:

Bravo

AF:

0.000144

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.000397

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000595

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 06, 2021

The c.872G>A (p.R291Q) 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 872, causing the arginine (R) at amino acid position 291 to be replaced by a glutamine (Q). 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

0.090

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0013

T;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.34

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.84

T;D

M_CAP

Benign

0.057

MetaRNN

Benign

0.038

T;T

MetaSVM

Uncertain

0.023

MutationAssessor

Benign

1.3

L;.

MutationTaster

Benign

0.62

D;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.56

N;N

REVEL

Benign

0.20

Sift

Benign

0.41

T;T

Sift4G

Benign

0.67

T;T

Polyphen

0.022

B;P

Vest4

0.14

MVP

0.49

MPC

0.059

ClinPred

0.039

GERP RS

3.4

Varity_R

0.045

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