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GeneBe

16-12704929-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018340.3(CPPED1):c.410A>T(p.Glu137Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CPPED1
NM_018340.3 missense

Scores

1
11
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.10
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CPPED1NM_018340.3 linkuse as main transcriptc.410A>T p.Glu137Val missense_variant 3/4 ENST00000381774.9
CPPED1NM_001099455.2 linkuse as main transcriptc.290-39814A>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CPPED1ENST00000381774.9 linkuse as main transcriptc.410A>T p.Glu137Val missense_variant 3/41 NM_018340.3 P1Q9BRF8-1
CPPED1ENST00000433677.6 linkuse as main transcriptc.290-39814A>T intron_variant 1 Q9BRF8-2
CPPED1ENST00000261660.4 linkuse as main transcriptc.290-39909A>T intron_variant 2 Q9BRF8-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249432
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135346
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000167
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461894
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsFeb 05, 2024The c.410A>T (p.E137V) alteration is located in exon 3 (coding exon 3) of the CPPED1 gene. This alteration results from a A to T substitution at nucleotide position 410, causing the glutamic acid (E) at amino acid position 137 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
0.18
BayesDel_addAF
Benign
-0.087
T
BayesDel_noAF
Benign
-0.10
Cadd
Benign
23
Dann
Uncertain
0.99
DEOGEN2
Benign
0.27
T
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.86
D
M_CAP
Uncertain
0.11
D
MetaRNN
Uncertain
0.74
D
MetaSVM
Uncertain
0.31
D
MutationAssessor
Uncertain
2.1
M
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Benign
0.40
T
PROVEAN
Pathogenic
-4.8
D
REVEL
Uncertain
0.53
Sift
Uncertain
0.011
D
Sift4G
Benign
0.16
T
Polyphen
0.80
P
Vest4
0.68
MutPred
0.53
Loss of disorder (P = 0.0093);
MVP
0.56
MPC
0.13
ClinPred
0.58
D
GERP RS
5.6
Varity_R
0.52
gMVP
0.54

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.

Other links and lift over

dbSNP: rs775720619; hg19: chr16-12798786; API