rs528748445
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001611.5(ACP5):c.238G>A(p.Asp80Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,614,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001611.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACP5 | NM_001611.5 | c.238G>A | p.Asp80Asn | missense_variant | 2/5 | ENST00000648477.1 | |
LOC124904638 | XR_007067140.1 | n.105+1727C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACP5 | ENST00000648477.1 | c.238G>A | p.Asp80Asn | missense_variant | 2/5 | NM_001611.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152148Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251448Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135916
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461868Hom.: 0 Cov.: 34 AF XY: 0.00000825 AC XY: 6AN XY: 727230
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152266Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74442
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 25, 2022 | The c.238G>A (p.D80N) alteration is located in exon 4 (coding exon 1) of the ACP5 gene. This alteration results from a G to A substitution at nucleotide position 238, causing the aspartic acid (D) at amino acid position 80 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Spondyloenchondrodysplasia with immune dysregulation Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 02, 2022 | This sequence change replaces aspartic acid with asparagine at codon 80 of the ACP5 protein (p.Asp80Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs528748445, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ACP5-related conditions. ClinVar contains an entry for this variant (Variation ID: 566480). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at