Variant 16-12705010-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018340.3(CPPED1):c.329G>A(p.Arg110Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00189 in 1,613,622 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 2 hom. )

Consequence

CPPED1
NM_018340.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.667

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007843196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPPED1	NM_018340.3 linkuse as main transcript	c.329G>A	p.Arg110Gln	missense_variant	3/4	ENST00000381774.9
CPPED1	NM_001099455.2 linkuse as main transcript	c.290-39895G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPPED1	ENST00000381774.9 linkuse as main transcript	c.329G>A	p.Arg110Gln	missense_variant	3/4	1	NM_018340.3	P1	Q9BRF8-1
CPPED1	ENST00000433677.6 linkuse as main transcript	c.290-39895G>A		intron_variant		1			Q9BRF8-2
CPPED1	ENST00000261660.4 linkuse as main transcript	c.290-39990G>A		intron_variant		2			Q9BRF8-3

Frequencies

GnomAD3 genomes

AF:

0.00133

AC:

203

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00216

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00147

AC:

366

AN:

248288

Hom.:

AF XY:

0.00160

AC XY:

216

AN XY:

134762

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.000725

Gnomad ASJ exome

AF:

0.00420

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00258

Gnomad FIN exome

AF:

0.000465

Gnomad NFE exome

AF:

0.00174

Gnomad OTH exome

AF:

0.00215

GnomAD4 exome

AF:

0.00194

AC:

2841

AN:

1461284

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

1449

AN XY:

726852

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000649

Gnomad4 ASJ exome

AF:

0.00341

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00231

Gnomad4 FIN exome

AF:

0.000562

Gnomad4 NFE exome

AF:

0.00215

Gnomad4 OTH exome

AF:

0.00161

GnomAD4 genome

AF:

0.00134

AC:

204

AN:

152338

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00216

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00181

Hom.:

Bravo

AF:

0.00125

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000240

AC:

ESP6500EA

AF:

0.00237

AC:

ExAC

AF:

0.00143

AC:

173

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00153

EpiControl

AF:

0.00184

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

Jul 25, 2023

The c.329G>A (p.R110Q) alteration is located in exon 3 (coding exon 3) of the CPPED1 gene. This alteration results from a G to A substitution at nucleotide position 329, causing the arginine (R) at amino acid position 110 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

0.080

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.41

Cadd

Benign

Dann

Benign

0.91

DEOGEN2

Benign

0.068

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.66

M_CAP

Benign

0.038

MetaRNN

Benign

0.0078

MetaSVM

Benign

-0.71

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.95

D;D;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.66

REVEL

Benign

0.17

Sift

Benign

0.36

Sift4G

Benign

0.63

Polyphen

0.015

Vest4

0.089

MVP

0.34

MPC

0.062

ClinPred

0.0030

GERP RS

2.3

Varity_R

0.056

gMVP

0.37

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