chr9-94955258-CA-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001193329.3(AOPEP):c.1744del(p.Met582CysfsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,612,082 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000028 ( 0 hom. )
Consequence
AOPEP
NM_001193329.3 frameshift
NM_001193329.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.98
Genes affected
AOPEP (HGNC:1361): (aminopeptidase O (putative)) This gene encodes a member of the M1 zinc aminopeptidase family. The encoded protein is a zinc-dependent metallopeptidase that catalyzes the removal of an amino acid from the amino terminus of a protein or peptide. This protein may play a role in the generation of angiotensin IV. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
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Very rare variant in population databases, with high coverage;
PP5
?
Variant 9-94955258-CA-C is Pathogenic according to our data. Variant chr9-94955258-CA-C is described in ClinVar as [Pathogenic]. Clinvar id is 1319963.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AOPEP | NM_001193329.3 | c.1744del | p.Met582CysfsTer6 | frameshift_variant | 8/17 | ENST00000375315.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AOPEP | ENST00000375315.8 | c.1744del | p.Met582CysfsTer6 | frameshift_variant | 8/17 | 1 | NM_001193329.3 | P1 | |
AOPEP | ENST00000297979.9 | c.1447del | p.Met483CysfsTer6 | frameshift_variant | 6/15 | 1 | |||
AOPEP | ENST00000462125.5 | n.410del | non_coding_transcript_exon_variant | 3/10 | 3 | ||||
AOPEP | ENST00000479161.5 | n.466del | non_coding_transcript_exon_variant | 4/11 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152222Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000200 AC: 5AN: 250370Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135280
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GnomAD4 exome AF: 0.0000281 AC: 41AN: 1459860Hom.: 0 Cov.: 29 AF XY: 0.0000248 AC XY: 18AN XY: 726334
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Dystonia 31 Pathogenic:2
Pathogenic, criteria provided, single submitter | not provided | Institute of Human Genetics, University Hospital of Duesseldorf | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 28, 2022 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at