The p.Arg42X (NM_175073.2 c.124C>T) variant in APTX has not been reported in ind ividuals with clinical features of ataxia with oculomotor apraxia type 1. This v ariant has been identified in 3/11578 of Latino chromosomes by the Exome Aggrega tion Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs201912053). This nonsense variant leads to a premature termination codon at position 42, which is predicted to lead to a truncated or absent protein. Biallelic loss of function of the APTX gene has been associated with ataxia with oculomotor apraxia type 1. In summary, although additional studies are required to fully establish a null effect on the protein, the p.Arg42X variant in APTX is likely pathogenic for ata xia with oculomotor apraxia type 1 in an autosomal recessive manner based upon p redicted impact on protein function.
ClinVar Genomic variation as it relates to human health
NM_001195248.2(APTX):c.124C>T (p.Arg42Ter)
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.
(5)
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
5
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.124C>T (p.Arg42Ter)
Variation ID: 420789 Accession: VCV000420789.28
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9p21.1 9: 32989768 (GRCh38) [ NCBI UCSC ] 9: 32989766 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Apr 27, 2017 Oct 20, 2024 Sep 14, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001195248.2:c.124C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001182177.2:p.Arg42Ter nonsense NM_001195249.2:c.124C>T NP_001182178.1:p.Arg42Ter nonsense NM_001195250.2:c.124C>T NP_001182179.2:p.Arg42Ter nonsense NM_001195251.2:c.124C>T NP_001182180.1:p.Arg42Ter nonsense NM_001195252.2:c.124C>T NP_001182181.2:p.Arg42Ter nonsense NM_001195254.2:c.124C>T NP_001182183.1:p.Arg42Ter nonsense NM_001368995.1:c.124C>T NP_001355924.1:p.Arg42Ter nonsense NM_001368996.1:c.124C>T NP_001355925.1:p.Arg42Ter nonsense NM_001368997.1:c.124C>T NP_001355926.1:p.Arg42Ter nonsense NM_001368998.1:c.124C>T NP_001355927.1:p.Arg42Ter nonsense NM_001368999.1:c.124C>T NP_001355928.1:p.Arg42Ter nonsense NM_001369000.1:c.124C>T NP_001355929.1:p.Arg42Ter nonsense NM_001369001.1:c.124C>T NP_001355930.1:p.Arg42Ter nonsense NM_001369002.1:c.-136C>T 5 prime UTR NM_001369003.1:c.-136C>T 5 prime UTR NM_001369004.1:c.-94C>T 5 prime UTR NM_001369005.1:c.-136C>T 5 prime UTR NM_001369006.1:c.-136C>T 5 prime UTR NM_001370669.1:c.-136C>T 5 prime UTR NM_001370670.1:c.-136C>T 5 prime UTR NM_001370673.1:c.-136C>T 5 prime UTR NM_175069.3:c.124C>T NP_778239.2:p.Arg42Ter nonsense NM_175073.3:c.124C>T NP_778243.1:p.Arg42Ter nonsense NR_036577.2:n.190C>T non-coding transcript variant NR_160920.1:n.190C>T non-coding transcript variant NR_160921.1:n.214C>T non-coding transcript variant NR_160922.1:n.445C>T non-coding transcript variant NR_160923.1:n.249C>T non-coding transcript variant NR_160924.1:n.249C>T non-coding transcript variant NR_160925.1:n.445C>T non-coding transcript variant NR_160926.1:n.249C>T non-coding transcript variant NR_160927.1:n.445C>T non-coding transcript variant NR_160928.1:n.445C>T non-coding transcript variant NR_160929.1:n.249C>T non-coding transcript variant NR_160930.1:n.190C>T non-coding transcript variant NR_160931.1:n.424C>T non-coding transcript variant NC_000009.12:g.32989768G>A NC_000009.11:g.32989766G>A NG_012821.2:g.40364C>T - Protein change
- R42*
- Other names
- -
- Canonical SPDI
- NC_000009.12:32989767: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.
-
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00004
- 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 |
289 | 358 | |
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. |
|---|---|---|---|---|
| Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Sep 14, 2023 | RCV000480449.26 | |
| Likely pathogenic (1) |
criteria provided, single submitter
|
Jan 3, 2017 | RCV000616687.5 |
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. |
|
|---|---|---|---|---|---|
|
Likely pathogenic
(Jan 03, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia
(Autosomal recessive inheritance)
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000731377.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Comment:
The p.Arg42X (NM_175073.2 c.124C>T) variant in APTX has not been reported in ind ividuals with clinical features of ataxia with oculomotor apraxia type 1. This … (more)
The p.Arg42X (NM_175073.2 c.124C>T) variant in APTX has not been reported in ind ividuals with clinical features of ataxia with oculomotor apraxia type 1. This v ariant has been identified in 3/11578 of Latino chromosomes by the Exome Aggrega tion Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs201912053). This nonsense variant leads to a premature termination codon at position 42, which is predicted to lead to a truncated or absent protein. Biallelic loss of function of the APTX gene has been associated with ataxia with oculomotor apraxia type 1. In summary, although additional studies are required to fully establish a null effect on the protein, the p.Arg42X variant in APTX is likely pathogenic for ata xia with oculomotor apraxia type 1 in an autosomal recessive manner based upon p redicted impact on protein function. (less)
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Jun 17, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001762165.1
First in ClinVar: Jul 30, 2021 Last updated: Jul 30, 2021 |
Clinical Features:
Cerebellar ataxia (present) , Cognitive impairment (present)
Sex: male
|
|
|
Likely pathogenic
(Jul 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000569761.7
First in ClinVar: Apr 27, 2017 Last updated: Mar 04, 2023 |
Comment:
Reported as a single heterozygous variant in a newborn undergoing exome sequencing through the BabySeq Project (Ceyhan-Birsoy et al., 2019); Nonsense variant predicted to result … (more)
Reported as a single heterozygous variant in a newborn undergoing exome sequencing through the BabySeq Project (Ceyhan-Birsoy et al., 2019); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 30609409) (less)
|
|
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Likely pathogenic
(Sep 14, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Athena Diagnostics
Accession: SCV004229969.1
First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024 |
Comment:
This variant is expected to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with … (more)
This variant is expected to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). (less)
|
|
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Pathogenic
(Mar 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV002498023.18
First in ClinVar: Apr 08, 2022 Last updated: Oct 20, 2024 |
Comment:
APTX: PVS1, PM2, PM3:Supporting
Number of individuals with the variant: 1
|
Comment:
Comment:
Reported as a single heterozygous variant in a newborn undergoing exome sequencing through the BabySeq Project (Ceyhan-Birsoy et al., 2019); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 30609409)
Comment:
This variant is expected to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org).
Comment:
APTX: PVS1, PM2, PM3:Supporting
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:
The p.Arg42X (NM_175073.2 c.124C>T) variant in APTX has not been reported in ind ividuals with clinical features of ataxia with oculomotor apraxia type 1. This v ariant has been identified in 3/11578 of Latino chromosomes by the Exome Aggrega tion Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs201912053). This nonsense variant leads to a premature termination codon at position 42, which is predicted to lead to a truncated or absent protein. Biallelic loss of function of the APTX gene has been associated with ataxia with oculomotor apraxia type 1. In summary, although additional studies are required to fully establish a null effect on the protein, the p.Arg42X variant in APTX is likely pathogenic for ata xia with oculomotor apraxia type 1 in an autosomal recessive manner based upon p redicted impact on protein function.
Comment:
Reported as a single heterozygous variant in a newborn undergoing exome sequencing through the BabySeq Project (Ceyhan-Birsoy et al., 2019); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 30609409)
Comment:
This variant is expected to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org).
Comment:
APTX: PVS1, PM2, PM3:Supporting
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Interpretation of Genomic Sequencing Results in Healthy and Ill Newborns: Results from the BabySeq Project. | Ceyhan-Birsoy O | American journal of human genetics | 2019 | PMID: 30609409 |
Text-mined citations for rs201912053 ...
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 Oct 20, 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.