rs199580546
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001611.5(ACP5):c.386G>A(p.Arg129His) variant causes a missense change. The variant allele was found at a frequency of 0.0000595 in 1,614,018 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R129C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001611.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACP5 | NM_001611.5 | c.386G>A | p.Arg129His | missense_variant | 3/5 | ENST00000648477.1 | |
LOC124904638 | XR_007067140.1 | n.105+1366C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACP5 | ENST00000648477.1 | c.386G>A | p.Arg129His | missense_variant | 3/5 | NM_001611.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152024Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251492Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135920
GnomAD4 exome AF: 0.0000609 AC: 89AN: 1461876Hom.: 0 Cov.: 33 AF XY: 0.0000715 AC XY: 52AN XY: 727238
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74372
ClinVar
Submissions by phenotype
Spondyloenchondrodysplasia with immune dysregulation Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 03, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 129 of the ACP5 protein (p.Arg129His). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ACP5 protein function. ClinVar contains an entry for this variant (Variation ID: 464889). This variant has not been reported in the literature in individuals affected with ACP5-related conditions. This variant is present in population databases (rs199580546, gnomAD 0.01%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at