3-132337486-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001099.5(ACP3):​c.487C>T​(p.Arg163Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000108 in 1,610,938 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

ACP3
NM_001099.5 missense

Scores

7
3
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.03
Variant links:
Genes affected
ACP3 (HGNC:125): (acid phosphatase 3) This gene encodes an enzyme that catalyzes the conversion of orthophosphoric monoester to alcohol and orthophosphate. It is synthesized under androgen regulation and is secreted by the epithelial cells of the prostate gland. An alternatively spliced transcript variant encoding a longer isoform has been found for this gene. This isoform contains a transmembrane domain and is localized in the plasma membrane-endosomal-lysosomal pathway. [provided by RefSeq, Sep 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07170203).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACP3NM_001099.5 linkc.487C>T p.Arg163Cys missense_variant Exon 5 of 10 ENST00000336375.10 NP_001090.2 P15309-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACP3ENST00000336375.10 linkc.487C>T p.Arg163Cys missense_variant Exon 5 of 10 1 NM_001099.5 ENSP00000337471.5 P15309-1

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152176
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00186
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000139
AC:
35
AN:
251200
Hom.:
0
AF XY:
0.000199
AC XY:
27
AN XY:
135754
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:
0.000948
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000490
GnomAD4 exome
AF:
0.000109
AC:
159
AN:
1458644
Hom.:
1
Cov.:
29
AF XY:
0.000153
AC XY:
111
AN XY:
725328
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00108
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000991
Gnomad4 OTH exome
AF:
0.000282
GnomAD4 genome
AF:
0.0000985
AC:
15
AN:
152294
Hom.:
0
Cov.:
33
AF XY:
0.000161
AC XY:
12
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00187
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000987
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.000206
AC:
25
Asia WGS
AF:
0.00173
AC:
6
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.487C>T (p.R163C) alteration is located in exon 5 (coding exon 5) of the ACPP gene. This alteration results from a C to T substitution at nucleotide position 487, causing the arginine (R) at amino acid position 163 to be replaced by a cysteine (C). 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
Uncertain
0.41
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.36
T;T;.
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.82
T;T;T
M_CAP
Benign
0.050
D
MetaRNN
Benign
0.072
T;T;T
MetaSVM
Benign
-0.48
T
MutationAssessor
Pathogenic
3.4
M;.;M
PrimateAI
Benign
0.32
T
PROVEAN
Pathogenic
-5.9
D;D;D
REVEL
Uncertain
0.36
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0010
D;D;D
Polyphen
1.0
D;.;D
Vest4
0.54
MVP
0.29
MPC
0.20
ClinPred
0.36
T
GERP RS
5.6
Varity_R
0.81
gMVP
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs554954787; hg19: chr3-132056330; API