dbSNP rs1555482097: CPPED1:p.Thr255Ser (chr16-12665068-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_018340.3(CPPED1):c.763A>T(p.Thr255Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CPPED1
NM_018340.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.02

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=0.053969055).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPPED1	NM_018340.3 link	c.763A>T	p.Thr255Ser	missense_variant	Exon 4 of 4	ENST00000381774.9	NP_060810.2	Q9BRF8-1
CPPED1	NM_001099455.2 link	c.337A>T	p.Thr113Ser	missense_variant	Exon 3 of 3		NP_001092925.1	Q9BRF8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CPPED1	ENST00000381774.9 link	c.763A>T	p.Thr255Ser	missense_variant	Exon 4 of 4	1	NM_018340.3	ENSP00000371193.4	Q9BRF8-1
CPPED1	ENST00000433677.6 link	c.337A>T	p.Thr113Ser	missense_variant	Exon 3 of 3	1		ENSP00000411127.2	Q9BRF8-2
CPPED1	ENST00000261660.4 link	c.290-48A>T		intron_variant	Intron 2 of 2	2		ENSP00000261660.4	Q9BRF8-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000412

AC:

AN:

242718

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132304

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000898

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455760

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724632

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0013

T;.

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.098

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.072

MetaRNN

Benign

0.054

T;T

MetaSVM

Benign

-0.31

MutationAssessor

Benign

0.55

N;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.90

N;N

REVEL

Benign

0.064

Sift

Benign

0.40

T;T

Sift4G

Benign

0.42

T;T

Polyphen

0.0020

B;P

Vest4

0.030

MutPred

0.29

Gain of relative solvent accessibility (P = 0.0215);.;

MVP

0.59

MPC

0.049

ClinPred

0.072

GERP RS

0.16

Varity_R

0.044

gMVP

0.32

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