Genetic Variant CPPED1:p.Leu295Val (chr16-12664948-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018340.3(CPPED1):c.883C>G(p.Leu295Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,108 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: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CPPED1
NM_018340.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.514

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4119162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPPED1	NM_018340.3 link	c.883C>G	p.Leu295Val	missense_variant	Exon 4 of 4	ENST00000381774.9	NP_060810.2	Q9BRF8-1
CPPED1	NM_001099455.2 link	c.457C>G	p.Leu153Val	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.883C>G	p.Leu295Val	missense_variant	Exon 4 of 4	1	NM_018340.3	ENSP00000371193.4	Q9BRF8-1
CPPED1	ENST00000433677.6 link	c.457C>G	p.Leu153Val	missense_variant	Exon 3 of 3	1		ENSP00000411127.2	Q9BRF8-2
CPPED1	ENST00000261660.4 link	c.362C>G	p.Ser121Cys	missense_variant	Exon 3 of 3	2		ENSP00000261660.4	Q9BRF8-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459108

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725982

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.883C>G (p.L295V) alteration is located in exon 4 (coding exon 4) of the CPPED1 gene. This alteration results from a C to G substitution at nucleotide position 883, causing the leucine (L) at amino acid position 295 to be replaced by a valine (V). 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

0.14

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0070

T;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.29

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.41

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-2.2

N;N

REVEL

Uncertain

0.56

Sift

Benign

0.055

T;D

Sift4G

Benign

0.085

T;D

Polyphen

0.88

P;D

Vest4

0.44

MutPred

0.59

Gain of sheet (P = 0.0344);.;

MVP

0.44

MPC

0.085

ClinPred

0.65

GERP RS

-2.6

Varity_R

0.089

gMVP

0.45

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over