rs879255600
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Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_001611.5(ACP5):c.816_817insC(p.Lys273GlnfsTer14) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
ACP5
NM_001611.5 frameshift
NM_001611.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.159
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 Likely_pathogenic. Variant got 7 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.166 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 19-11575171-T-TG is Pathogenic according to our data. Variant chr19-11575171-T-TG is described in ClinVar as [Pathogenic]. Clinvar id is 225658.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACP5 | NM_001611.5 | c.816_817insC | p.Lys273GlnfsTer14 | frameshift_variant | 5/5 | ENST00000648477.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACP5 | ENST00000648477.1 | c.816_817insC | p.Lys273GlnfsTer14 | frameshift_variant | 5/5 | NM_001611.5 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251178Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135836
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461844Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727216
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GnomAD4 genome ? Cov.: 31
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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 | Aug 25, 2017 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at