rs387906668
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_001611.5(ACP5):c.266C>T(p.Thr89Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,872 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 Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
ACP5
NM_001611.5 missense
NM_001611.5 missense
Scores
8
5
1
Clinical Significance
Conservation
PhyloP100: 8.94
Genes affected
ACP5 (HGNC:124): (acid phosphatase 5, tartrate resistant) This gene encodes an iron containing glycoprotein which catalyzes the conversion of orthophosphoric monoester to alcohol and orthophosphate. It is the most basic of the acid phosphatases and is the only form not inhibited by L(+)-tartrate. [provided by RefSeq, Aug 2008]
ZNF627 (HGNC:30570): (zinc finger protein 627) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.889
PP5
?
Variant 19-11576839-G-A is Pathogenic according to our data. Variant chr19-11576839-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 29829.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-11576839-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACP5 | NM_001611.5 | c.266C>T | p.Thr89Ile | missense_variant | 3/5 | ENST00000648477.1 | |
LOC124904638 | XR_007067140.1 | n.105+1486G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACP5 | ENST00000648477.1 | c.266C>T | p.Thr89Ile | missense_variant | 3/5 | NM_001611.5 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461872Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727238
GnomAD4 exome
AF:
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1
AN:
1461872
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
727238
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Spondyloenchondrodysplasia with immune dysregulation Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2011 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;D;D;D;D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M;M;M;M;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
Polyphen
D;D;D;D;D;.
Vest4
0.80, 0.80
MutPred
Loss of disorder (P = 0.0446);Loss of disorder (P = 0.0446);Loss of disorder (P = 0.0446);Loss of disorder (P = 0.0446);Loss of disorder (P = 0.0446);Loss of disorder (P = 0.0446);
MVP
0.97
MPC
1.1
ClinPred
D
GERP RS
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