19-50790612-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_033068.3(ACP4):​c.130C>T​(p.Arg44Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000709 in 1,551,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

ACP4
NM_033068.3 missense

Scores

11
6
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.961
Variant links:
Genes affected
ACP4 (HGNC:14376): (acid phosphatase 4) Acid phosphatases are enzymes capable of hydrolyzing orthophosphoric acid esters in an acid medium. This gene is up-regulated by androgens and is down-regulated by estrogens in the prostate cancer cell line. This gene exhibits a lower level of expression in testicular cancer tissues than in normal tissues. The protein encoded by this gene has structural similarity to prostatic and lysosomal acid phosphatases. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]
SMIM47 (HGNC:53452): (small integral membrane protein 47)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.987

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACP4NM_033068.3 linkc.130C>T p.Arg44Trp missense_variant Exon 2 of 11 ENST00000270593.2 NP_149059.1
LOC105372439XR_936026.3 linkn.435-897G>A intron_variant Intron 2 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACP4ENST00000270593.2 linkc.130C>T p.Arg44Trp missense_variant Exon 2 of 11 1 NM_033068.3 ENSP00000270593.1 Q9BZG2-1
SMIM47ENST00000636757.1 linkc.-59-897G>A intron_variant Intron 2 of 4 5 ENSP00000489695.1 A0A1B0GTG8

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152104
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000500
AC:
7
AN:
1399076
Hom.:
0
Cov.:
34
AF XY:
0.00000290
AC XY:
2
AN XY:
690386
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000276
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000215
Gnomad4 NFE exome
AF:
0.00000463
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152104
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74292
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 22, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.130C>T (p.R44W) alteration is located in exon 2 (coding exon 2) of the ACPT gene. This alteration results from a C to T substitution at nucleotide position 130, causing the arginine (R) at amino acid position 44 to be replaced by a tryptophan (W). 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
Pathogenic
0.89
BayesDel_addAF
Pathogenic
0.40
D
BayesDel_noAF
Pathogenic
0.33
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.45
T
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Benign
0.37
N
LIST_S2
Uncertain
0.95
D
M_CAP
Pathogenic
0.47
D
MetaRNN
Pathogenic
0.99
D
MetaSVM
Uncertain
0.10
D
MutationAssessor
Pathogenic
4.7
H
PrimateAI
Pathogenic
0.82
D
PROVEAN
Pathogenic
-7.0
D
REVEL
Pathogenic
0.86
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.71
MutPred
0.98
Loss of disorder (P = 0.0254);
MVP
0.94
MPC
0.57
ClinPred
1.0
D
GERP RS
3.4
Varity_R
0.80
gMVP
0.97

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs1319966793; hg19: chr19-51293869; API