Variant 16-12704987-C-A 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.352G>T(p.Ala118Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000601 in 1,614,200 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

CPPED1
NM_018340.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.76

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=0.028403908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPPED1	NM_018340.3 linkuse as main transcript	c.352G>T	p.Ala118Ser	missense_variant	3/4	ENST00000381774.9	NP_060810.2
CPPED1	NM_001099455.2 linkuse as main transcript	c.290-39872G>T		intron_variant			NP_001092925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPPED1	ENST00000381774.9 linkuse as main transcript	c.352G>T	p.Ala118Ser	missense_variant	3/4	1	NM_018340.3	ENSP00000371193	P1	Q9BRF8-1
CPPED1	ENST00000433677.6 linkuse as main transcript	c.290-39872G>T		intron_variant		1		ENSP00000411127		Q9BRF8-2
CPPED1	ENST00000261660.4 linkuse as main transcript	c.290-39967G>T		intron_variant		2		ENSP00000261660		Q9BRF8-3

Frequencies

GnomAD3 genomes

AF:

0.000348

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000803

AC:

AN:

249142

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

135204

show subpopulations

Gnomad AFR exome

AF:

0.00116

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.000348

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000846

Hom.:

Bravo

AF:

0.000325

ESP6500AA

AF:

0.00119

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

AC:

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

Oct 05, 2023

The c.352G>T (p.A118S) alteration is located in exon 3 (coding exon 3) of the CPPED1 gene. This alteration results from a G to T substitution at nucleotide position 352, causing the alanine (A) at amino acid position 118 to be replaced by a serine (S). 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

0.069

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.045

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.66

M_CAP

Benign

0.022

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.61

MutationAssessor

Benign

-1.2

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Benign

0.24

PROVEAN

Benign

1.4

REVEL

Benign

0.24

Sift

Benign

0.40

Sift4G

Benign

0.71

Polyphen

0.0010

Vest4

0.089

MVP

0.42

MPC

0.050

ClinPred

0.054

GERP RS

5.7

Varity_R

0.10

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