Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000012, PM2_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
ClinVar Genomic variation as it relates to human health
NM_001195248.2(APTX):c.388C>T (p.Gln130Ter)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(2)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic/Likely pathogenic
2
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001195248.2(APTX):c.388C>T (p.Gln130Ter)
Variation ID: 1333290 Accession: VCV001333290.5
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9p21.1 9: 32987639 (GRCh38) [ NCBI UCSC ] 9: 32987637 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jan 15, 2022 Feb 28, 2024 Dec 7, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001195248.2:c.388C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001182177.2:p.Gln130Ter nonsense NM_001195249.2:c.388C>T NP_001182178.1:p.Gln130Ter nonsense NM_001195250.2:c.226C>T NP_001182179.2:p.Gln76Ter nonsense NM_001195251.2:c.388C>T NP_001182180.1:p.Gln130Ter nonsense NM_001195252.2:c.267+121C>T intron variant NM_001195254.2:c.226C>T NP_001182183.1:p.Gln76Ter nonsense NM_001368995.1:c.388C>T NP_001355924.1:p.Gln130Ter nonsense NM_001368996.1:c.388C>T NP_001355925.1:p.Gln130Ter nonsense NM_001368997.1:c.388C>T NP_001355926.1:p.Gln130Ter nonsense NM_001368998.1:c.388C>T NP_001355927.1:p.Gln130Ter nonsense NM_001368999.1:c.388C>T NP_001355928.1:p.Gln130Ter nonsense NM_001369000.1:c.226C>T NP_001355929.1:p.Gln76Ter nonsense NM_001369001.1:c.226C>T NP_001355930.1:p.Gln76Ter nonsense NM_001369002.1:c.124C>T NP_001355931.1:p.Gln42Ter nonsense NM_001369003.1:c.124C>T NP_001355932.1:p.Gln42Ter nonsense NM_001369004.1:c.124C>T NP_001355933.1:p.Gln42Ter nonsense NM_001369005.1:c.124C>T NP_001355934.1:p.Gln42Ter nonsense NM_001369006.1:c.124C>T NP_001355935.1:p.Gln42Ter nonsense NM_001370669.1:c.124C>T NP_001357598.1:p.Gln42Ter nonsense NM_001370670.1:c.124C>T NP_001357599.1:p.Gln42Ter nonsense NM_001370673.1:c.124C>T NP_001357602.1:p.Gln42Ter nonsense NM_175069.3:c.388C>T NP_778239.2:p.Gln130Ter nonsense NM_175073.3:c.388C>T NP_778243.1:p.Gln130Ter nonsense NR_036577.2:n.339C>T non-coding transcript variant NR_160920.1:n.454C>T non-coding transcript variant NR_160921.1:n.358C>T non-coding transcript variant NR_160922.1:n.589C>T non-coding transcript variant NR_160923.1:n.393C>T non-coding transcript variant NR_160924.1:n.398C>T non-coding transcript variant NR_160925.1:n.594C>T non-coding transcript variant NR_160926.1:n.384C>T non-coding transcript variant NR_160927.1:n.704C>T non-coding transcript variant NR_160928.1:n.594C>T non-coding transcript variant NR_160929.1:n.508C>T non-coding transcript variant NR_160930.1:n.334C>T non-coding transcript variant NR_160931.1:n.573C>T non-coding transcript variant NC_000009.12:g.32987639G>A NC_000009.11:g.32987637G>A NG_012821.2:g.42493C>T - Protein change
- Q130*, Q42*, Q76*
- Other names
- -
- Canonical SPDI
- NC_000009.12:32987638:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| APTX | - | - |
GRCh38 GRCh37 |
291 | 360 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Likely pathogenic (1) |
criteria provided, single submitter
|
Jan 3, 2022 | RCV001807978.1 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Dec 7, 2023 | RCV001869577.4 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
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Likely pathogenic
(Jan 03, 2022)
|
criteria provided, single submitter
Method: clinical testing
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Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia
Affected status: yes
Allele origin:
germline
|
3billion
Accession: SCV002058308.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
Comment:
Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are … (more)
Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000012, PM2_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Muscular dystrophy (present) , Myopathy (present)
|
|
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Pathogenic
(Dec 07, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002142247.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln130*) in the APTX gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln130*) in the APTX gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APTX are known to be pathogenic (PMID: 15719174, 21465257, 23183622, 26285866). This variant is present in population databases (no rsID available, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with autosomal recessive ataxia with oculomotor apraxia type 1 (PMID: 28516743). ClinVar contains an entry for this variant (Variation ID: 1333290). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
|
Comment:
Comment:
This sequence change creates a premature translational stop signal (p.Gln130*) in the APTX gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APTX are known to be pathogenic (PMID: 15719174, 21465257, 23183622, 26285866). This variant is present in population databases (no rsID available, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with autosomal recessive ataxia with oculomotor apraxia type 1 (PMID: 28516743). ClinVar contains an entry for this variant (Variation ID: 1333290). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000012, PM2_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
Comment:
This sequence change creates a premature translational stop signal (p.Gln130*) in the APTX gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APTX are known to be pathogenic (PMID: 15719174, 21465257, 23183622, 26285866). This variant is present in population databases (no rsID available, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with autosomal recessive ataxia with oculomotor apraxia type 1 (PMID: 28516743). ClinVar contains an entry for this variant (Variation ID: 1333290). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| A Novel APTX Variant and Ataxia with Oculomotor Apraxia Type 1. | Manzoor H | Journal of clinical neurology (Seoul, Korea) | 2017 | PMID: 28516743 |
| Complete APTX deletion in a patient with ataxia with oculomotor apraxia type 1. | van Minkelen R | BMC medical genetics | 2015 | PMID: 26285866 |
| A novel mutation in the aprataxin (APTX) gene in an Iranian individual suffering early-onset ataxia with oculomotor apraxia type 1(AOA1) disease. | Nouri N | Iranian biomedical journal | 2012 | PMID: 23183622 |
| Ataxia with oculomotor apraxia type1 (AOA1): novel and recurrent aprataxin mutations, coenzyme Q10 analyses, and clinical findings in Italian patients. | Castellotti B | Neurogenetics | 2011 | PMID: 21465257 |
| The novel human gene aprataxin is directly involved in DNA single-strand-break repair. | Mosesso P | Cellular and molecular life sciences : CMLS | 2005 | PMID: 15719174 |
Text-mined citations for rs1225927323 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.