chr9-94800852-CT-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001193329.3(AOPEP):c.1215del(p.Val406CysfsTer14) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000601 in 1,614,216 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000063 ( 0 hom. )
Consequence
AOPEP
NM_001193329.3 frameshift
NM_001193329.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -2.36
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]
Genome browser will be placed here
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
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 9-94800852-CT-C is Pathogenic according to our data. Variant chr9-94800852-CT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1319962.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.1215del | p.Val406CysfsTer14 | frameshift_variant | 5/17 | ENST00000375315.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AOPEP | ENST00000375315.8 | c.1215del | p.Val406CysfsTer14 | frameshift_variant | 5/17 | 1 | NM_001193329.3 | P1 | |
AOPEP | ENST00000297979.9 | c.1215del | p.Val406CysfsTer14 | frameshift_variant | 5/15 | 1 | |||
AOPEP | ENST00000277198.6 | c.1215del | p.Val406CysfsTer14 | frameshift_variant | 5/8 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152206Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
5
AN:
152206
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251418Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135876
GnomAD3 exomes
AF:
AC:
14
AN:
251418
Hom.:
AF XY:
AC XY:
9
AN XY:
135876
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000629 AC: 92AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.0000715 AC XY: 52AN XY: 727248
GnomAD4 exome
AF:
AC:
92
AN:
1461892
Hom.:
Cov.:
32
AF XY:
AC XY:
52
AN XY:
727248
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152324Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74484
GnomAD4 genome
?
AF:
AC:
5
AN:
152324
Hom.:
Cov.:
32
AF XY:
AC XY:
4
AN XY:
74484
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Dystonia 31 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 28, 2022 | - - |
AOPEP-related disorder Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 18, 2023 | The AOPEP c.1215delT variant is predicted to result in a frameshift and premature protein termination (p.Val406Cysfs*14). This variant was reported, along with another pathogenic variant, in an individual with dystonia (Zech et al. 2022. PubMed ID: 34596301). This variant is reported in 0.011% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-97563134-CT-C). Frameshift variants in AOPEP are expected to be pathogenic. This variant is interpreted as likely pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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