NM_001193329.3(AOPEP):c.1477C>T (p.Arg493Ter) AND Dystonia 31

Germline classification:: Pathogenic (2 submissions)
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001775036.3

Allele description [Variation Report for NM_001193329.3(AOPEP):c.1477C>T (p.Arg493Ter)]

NM_001193329.3(AOPEP):c.1477C>T (p.Arg493Ter)

Gene:

AOPEP:aminopeptidase O (putative) [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q22.32

Genomic location:

Preferred name:

NM_001193329.3(AOPEP):c.1477C>T (p.Arg493Ter)

Other names:

AOPEP, ARG493TER (rs577000059)

HGVS:

NC_000009.12:g.94924098C>T
NG_027833.1:g.202430C>T
NM_001193329.3:c.1477C>TMANE SELECT
NM_001193331.3:c.1477C>T
NM_001386061.1:c.372-31079C>T
NM_001386062.2:c.1156C>T
NM_001386063.2:c.1477C>T
NM_001386066.1:c.1477C>T
NM_001386067.1:c.1365-55269C>T
NM_001386068.1:c.1477C>T
NM_001386069.1:c.1365-31079C>T
NM_001386070.1:c.1477C>T
NM_001386071.1:c.1477C>T
NM_001386072.1:c.1477C>T
NM_001386073.1:c.607C>T
NM_001386074.1:c.1477C>T
NM_001386075.1:c.1477C>T
NM_001386076.1:c.1477C>T
NM_032823.6:c.1365-31079C>T
NP_001180258.1:p.Arg493Ter
NP_001180260.1:p.Arg493Ter
NP_001372991.1:p.Arg386Ter
NP_001372992.1:p.Arg493Ter
NP_001372995.1:p.Arg493Ter
NP_001372997.1:p.Arg493Ter
NP_001372999.1:p.Arg493Ter
NP_001373000.1:p.Arg493Ter
NP_001373001.1:p.Arg493Ter
NP_001373002.1:p.Arg203Ter
NP_001373003.1:p.Arg493Ter
NP_001373004.1:p.Arg493Ter
NP_001373005.1:p.Arg493Ter
NC_000009.11:g.97686380C>T
NM_001193329.1:c.1477C>T
NR_169862.1:n.1665C>T
NR_169865.1:n.1498C>T
NR_169867.1:n.241C>T

Protein change:

R203*; ARG493TER

Links:

OMIM: 619600.0001; dbSNP: rs577000059

NCBI 1000 Genomes Browser:

rs577000059

Molecular consequence:

NM_001386061.1:c.372-31079C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001386067.1:c.1365-55269C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001386069.1:c.1365-31079C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_032823.6:c.1365-31079C>T - intron variant - [Sequence Ontology: SO:0001627]
NR_169862.1:n.1665C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_169865.1:n.1498C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_169867.1:n.241C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001193329.3:c.1477C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001193331.3:c.1477C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386062.2:c.1156C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386063.2:c.1477C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386066.1:c.1477C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386068.1:c.1477C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386070.1:c.1477C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386071.1:c.1477C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386072.1:c.1477C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386073.1:c.607C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386074.1:c.1477C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386075.1:c.1477C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386076.1:c.1477C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Dystonia 31
Synonyms:: ZECH-BOESCH SYNDROME
Identifiers:: MONDO: MONDO:0030455; MedGen: C5562001; OMIM: 619565

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002011805	OMIM	no assertion criteria provided	Pathogenic (Jan 28, 2022)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV005416464	Juno Genomics, Hangzhou Juno Genomics, Inc	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002011805

OMIM

no assertion criteria provided

Pathogenic
(Jan 28, 2022)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV005416464

Juno Genomics, Hangzhou Juno Genomics, Inc

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Biallelic AOPEP Loss-of-Function Variants Cause Progressive Dystonia with Prominent Limb Involvement.

Zech M, Kumar KR, Reining S, Reunert J, Tchan M, Riley LG, Drew AP, Adam RJ, Berutti R, Biskup S, Derive N, Bakhtiari S, Jin SC, Kruer MC, Bardakjian T, Gonzalez-Alegre P, Keller Sarmiento IJ, Mencacci NE, Lubbe SJ, Kurian MA, Clot F, Méneret A, et al.

Mov Disord. 2022 Jan;37(1):137-147. doi: 10.1002/mds.28804. Epub 2021 Oct 1.

PubMed [citation]

PMID:: 34596301

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV002011805.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 13-year-old boy, born of unrelated Italian parents (family 1), with dystonia-31 (DYT31; 619565), Zech et al. (2022) identified a homozygous c.1477C-T transition (c.1477C-T, NM_001193329.1) in exon 5 of the AOPEP gene, resulting in an arg493-to-ter (R493X) substitution in the consensus zinc-binding motif. The mutation, which was found by trio-based whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The variant was found twice in the gnomAD database in only heterozygous state. Studies of the variant and studies of patient cells were not performed, but the variant was predicted to result in nonsense-mediated mRNA decay and a loss of function.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Juno Genomics, Hangzhou Juno Genomics, Inc, SCV005416464.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

PM2_Supporting+PVS1+PM3_Supporting+PP4

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 30, 2024

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