11-47245548-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001610.4(ACP2):c.475T>C(p.Cys159Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 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: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
ACP2
NM_001610.4 missense
NM_001610.4 missense
Scores
12
6
1
Clinical Significance
Conservation
PhyloP100: 8.48
Genes affected
ACP2 (HGNC:123): (acid phosphatase 2, lysosomal) The protein encoded by this gene belongs to the histidine acid phosphatase family, which hydrolyze orthophosphoric monoesters to alcohol and phosphate. This protein is localized to the lysosomal membrane, and is chemically and genetically distinct from the red cell acid phosphatase. Mice lacking this gene showed multiple defects, including bone structure alterations, lysosomal storage defects, and an increased tendency towards seizures. An enzymatically-inactive allele of this gene in mice showed severe growth retardation, hair-follicle abnormalities, and an ataxia-like phenotype. Alternatively spliced transcript variants have been found for this gene. A C-terminally extended isoform is also predicted to be produced by the use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism. [provided by RefSeq, Oct 2017]
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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, 0.978
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACP2 | NM_001610.4 | c.475T>C | p.Cys159Arg | missense_variant | 5/11 | ENST00000672073.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACP2 | ENST00000672073.1 | c.475T>C | p.Cys159Arg | missense_variant | 5/11 | NM_001610.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461890Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727248
GnomAD4 exome
AF:
AC:
1
AN:
1461890
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727248
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
Bravo
AF:
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 submitter | clinical testing | Ambry Genetics | Jan 03, 2024 | The c.475T>C (p.C159R) alteration is located in exon 5 (coding exon 5) of the ACP2 gene. This alteration results from a T to C substitution at nucleotide position 475, causing the cysteine (C) at amino acid position 159 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;D;D
Vest4
MutPred
Gain of disorder (P = 0.0062);.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at