ClinVar Genomic variation as it relates to human health
NM_001195248.2(APTX):c.596del (p.Arg199fs)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001195248.2(APTX):c.596del (p.Arg199fs)
Variation ID: 1323370 Accession: VCV001323370.6
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 9p21.1 9: 32984805 (GRCh38) [ NCBI UCSC ] 9: 32984803 (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 Nov 29, 2021 Jun 17, 2024 May 28, 2019 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001195248.2:c.596del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001182177.2:p.Arg199fs frameshift NM_001195249.2:c.596del NP_001182178.1:p.Arg199fs frameshift NM_001195250.2:c.434del NP_001182179.2:p.Arg145fs frameshift NM_001195251.2:c.596del NP_001182180.1:p.Arg199fs frameshift NM_001195252.2:c.380del NP_001182181.2:p.Arg127fs frameshift NM_001195254.2:c.434del NP_001182183.1:p.Arg145fs frameshift NM_001368995.1:c.596del NP_001355924.1:p.Arg199fs frameshift NM_001368996.1:c.596del NP_001355925.1:p.Arg199fs frameshift NM_001368997.1:c.596del NP_001355926.1:p.Arg199fs frameshift NM_001368998.1:c.596del NP_001355927.1:p.Arg199fs frameshift NM_001368999.1:c.596del NP_001355928.1:p.Arg199fs frameshift NM_001369000.1:c.434del NP_001355929.1:p.Arg145fs frameshift NM_001369001.1:c.434del NP_001355930.1:p.Arg145fs frameshift NM_001369002.1:c.332del NP_001355931.1:p.Arg111fs frameshift NM_001369003.1:c.332del NP_001355932.1:p.Arg111fs frameshift NM_001369004.1:c.332del NP_001355933.1:p.Arg111fs frameshift NM_001369005.1:c.332del NP_001355934.1:p.Arg111fs frameshift NM_001369006.1:c.332del NP_001355935.1:p.Arg111fs frameshift NM_001370669.1:c.332del NP_001357598.1:p.Arg111fs frameshift NM_001370670.1:c.332del NP_001357599.1:p.Arg111fs frameshift NM_001370673.1:c.332del NP_001357602.1:p.Arg111fs frameshift NM_175069.3:c.596del NP_778239.2:p.Arg199fs frameshift NM_175069.3:c.596delG NM_175073.3:c.596del NP_778243.1:p.Arg199fs frameshift NR_036577.2:n.547del non-coding transcript variant NR_160921.1:n.566del non-coding transcript variant NR_160922.1:n.797del non-coding transcript variant NR_160923.1:n.601del non-coding transcript variant NR_160924.1:n.606del non-coding transcript variant NR_160925.1:n.802del non-coding transcript variant NR_160926.1:n.592del non-coding transcript variant NR_160930.1:n.542del non-coding transcript variant NR_160931.1:n.781del non-coding transcript variant NC_000009.12:g.32984805del NC_000009.11:g.32984803del NG_012821.2:g.45327del - Protein change
- R111fs, R127fs, R145fs, R199fs
- Other names
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- Canonical SPDI
- NC_000009.12:32984804:C:
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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
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The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00002
- 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 | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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. |
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APTX | - | - |
GRCh38 GRCh37 |
285 | 353 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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May 28, 2019 | RCV001784753.7 |
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
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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
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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
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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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Pathogenic
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002018349.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Lifecell International Pvt. Ltd
Accession: SCV003845983.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023 |
Comment:
A Homozygote Frameshift variant c.596delG in Exon 6 of the APTX gene that results in the amino acid substitution p.Arg199fs*15 was identified. The observed variant … (more)
A Homozygote Frameshift variant c.596delG in Exon 6 of the APTX gene that results in the amino acid substitution p.Arg199fs*15 was identified. The observed variant has a minor allele frequency of 0.00002% in gnomAD exomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic (variant ID: 1323370). This variant was reported among the patients for ataxia with oculomotor apraxia (Renaud M et al., 2018). Based on the above evidence this variant has been classified as Pathogenic according to the ACMG guidelines. (less)
Ethnicity/Population group: Asian
Geographic origin: India
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV005060978.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
Comment:
The observed frameshift c.596del(p.Arg199LeufsTer15) variant in APTX gene has been reported previously in homozygous state in multiple individuals affected with early-onset ataxia with oculomotor apraxia … (more)
The observed frameshift c.596del(p.Arg199LeufsTer15) variant in APTX gene has been reported previously in homozygous state in multiple individuals affected with early-onset ataxia with oculomotor apraxia and hypoalbuminemia (Renaud M, et al., 2018). The p.Arg199LeufsTer15 variant has been reported with allele frequency of 0.002% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Pathogenic. This variant causes a frameshift starting with codon Arginine 199, changes this amino acid to Leucine residue, and creates a premature Stop codon at position 15 of the new reading frame, denoted p.Arg199LeufsTer15. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic. (less)
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Clinical, Biomarker, and Molecular Delineations and Genotype-Phenotype Correlations of Ataxia With Oculomotor Apraxia Type 1. | Renaud M | JAMA neurology | 2018 | PMID: 29356829 |
Text-mined citations for rs770007531 ...
HelpRecord last updated Jun 17, 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.