ClinVar Genomic variation as it relates to human health
NM_001195248.2(APTX):c.18G>T (p.Trp6Cys)
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.
Uncertain significance(9); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001195248.2(APTX):c.18G>T (p.Trp6Cys)
Variation ID: 214126 Accession: VCV000214126.23
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9p21.1 9: 32989874 (GRCh38) [ NCBI UCSC ] 9: 32989872 (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 May 29, 2016 Feb 14, 2024 Jul 10, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001195248.2:c.18G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001182177.2:p.Trp6Cys missense NM_001195249.2:c.18G>T NP_001182178.1:p.Trp6Cys missense NM_001195250.2:c.18G>T NP_001182179.2:p.Trp6Cys missense NM_001195251.2:c.18G>T NP_001182180.1:p.Trp6Cys missense NM_001195252.2:c.18G>T NP_001182181.2:p.Trp6Cys missense NM_001195254.2:c.18G>T NP_001182183.1:p.Trp6Cys missense NM_001368995.1:c.18G>T NP_001355924.1:p.Trp6Cys missense NM_001368996.1:c.18G>T NP_001355925.1:p.Trp6Cys missense NM_001368997.1:c.18G>T NP_001355926.1:p.Trp6Cys missense NM_001368998.1:c.18G>T NP_001355927.1:p.Trp6Cys missense NM_001368999.1:c.18G>T NP_001355928.1:p.Trp6Cys missense NM_001369000.1:c.18G>T NP_001355929.1:p.Trp6Cys missense NM_001369001.1:c.18G>T NP_001355930.1:p.Trp6Cys missense NM_001369002.1:c.-242G>T 5 prime UTR NM_001369003.1:c.-242G>T 5 prime UTR NM_001369004.1:c.-200G>T 5 prime UTR NM_001369005.1:c.-242G>T 5 prime UTR NM_001369006.1:c.-242G>T 5 prime UTR NM_001370669.1:c.-242G>T 5 prime UTR NM_001370670.1:c.-242G>T 5 prime UTR NM_001370673.1:c.-242G>T 5 prime UTR NM_175069.3:c.18G>T NP_778239.2:p.Trp6Cys missense NM_175073.3:c.18G>T NP_778243.1:p.Trp6Cys missense NR_036577.2:n.84G>T non-coding transcript variant NR_160920.1:n.84G>T non-coding transcript variant NR_160921.1:n.108G>T non-coding transcript variant NR_160922.1:n.339G>T non-coding transcript variant NR_160923.1:n.143G>T non-coding transcript variant NR_160924.1:n.143G>T non-coding transcript variant NR_160925.1:n.339G>T non-coding transcript variant NR_160926.1:n.143G>T non-coding transcript variant NR_160927.1:n.339G>T non-coding transcript variant NR_160928.1:n.339G>T non-coding transcript variant NR_160929.1:n.143G>T non-coding transcript variant NR_160930.1:n.84G>T non-coding transcript variant NR_160931.1:n.318G>T non-coding transcript variant NC_000009.12:g.32989874C>A NC_000009.11:g.32989872C>A NG_012821.2:g.40258G>T - Protein change
- W6C
- Other names
- p.W6C:TGG>TGT
- Canonical SPDI
- NC_000009.12:32989873:C: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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0.00020 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
Trans-Omics for Precision Medicine (TOPMed) 0.00034
The Genome Aggregation Database (gnomAD) 0.00042
The Genome Aggregation Database (gnomAD), exomes 0.00050
Exome Aggregation Consortium (ExAC) 0.00072
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
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. |
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APTX | - | - |
GRCh38 GRCh37 |
282 | 350 |
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. |
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Conflicting interpretations of pathogenicity (6) |
criteria provided, conflicting classifications
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Jul 10, 2023 | RCV000200146.27 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Jul 20, 2018 | RCV000357224.14 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jun 14, 2016 | RCV001844083.11 | |
Uncertain significance (1) |
criteria provided, single submitter
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Nov 1, 2021 | RCV002517195.8 |
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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Uncertain significance
(Jun 14, 2016)
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criteria provided, single submitter
Method: clinical testing
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Ataxia with Oculomotor Apraxia
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000479645.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Uncertain significance
(Feb 24, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000705962.2
First in ClinVar: Apr 02, 2018 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Uncertain significance
(Feb 08, 2018)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000883415.1
First in ClinVar: Dec 15, 2018 Last updated: Dec 15, 2018 |
Comment:
The APTX: c.18G>T; p.Trp6Cys variant (rs144076460; ClinVar Variation ID: 214126) has been previously reported in a cohort of patients with a clinical diagnosis of oculomotor … (more)
The APTX: c.18G>T; p.Trp6Cys variant (rs144076460; ClinVar Variation ID: 214126) has been previously reported in a cohort of patients with a clinical diagnosis of oculomotor apraxia type 1 (van Minkelen 2015). However, no other specific genotype or inheritance information was provided, and the authors considered this variant to be of uncertain clinical significance. This variant is listed in the Genome Aggregation Database (gnomAD) browser with a frequency in non-Finnish European populations of 0.1% (identified in 122 out of 126,606 chromosomes, including 1 homozygote). The tryptophan at codon 6 is highly conserved considering 12 species up to Baker’s yeast (Alamut software v2.9), and computational analyses suggest this variant has a significant effect on APTX protein structure/function (SIFT: damaging and PolyPhen2: probably damaging). However, based on the available information, the clinical significance of the p.Trp6Cys variant cannot be determined with certainty. (less)
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Uncertain significance
(Jan 13, 2018)
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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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Illumina Laboratory Services, Illumina
Accession: SCV000479644.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
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Uncertain significance
(Oct 23, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Athena Diagnostics Inc
Accession: SCV001475537.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
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Uncertain significance
(Jul 20, 2018)
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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: yes
Allele origin:
maternal
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Baylor Genetics
Accession: SCV001530662.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. These variants have been previously reported but pathogenicity of these … (more)
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. These variants have been previously reported but pathogenicity of these changes is unclear [PMID 26285866] (less)
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Uncertain significance
(Aug 26, 2019)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001713481.1
First in ClinVar: Jun 15, 2021 Last updated: Jun 15, 2021 |
Number of individuals with the variant: 1
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Uncertain significance
(Nov 01, 2021)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV003740352.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
The c.18G>T (p.W6C) alteration is located in exon 3 (coding exon 1) of the APTX gene. This alteration results from a G to T substitution … (more)
The c.18G>T (p.W6C) alteration is located in exon 3 (coding exon 1) of the APTX gene. This alteration results from a G to T substitution at nucleotide position 18, causing the tryptophan (W) at amino acid position 6 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
Number of individuals with the variant: 1
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Uncertain significance
(Nov 23, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000251157.12
First in ClinVar: Oct 11, 2015 Last updated: Mar 04, 2023 |
Comment:
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In-silico analysis is inconclusive as to whether the variant alters … (more)
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In-silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 26285866) (less)
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Likely benign
(Jul 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV003280380.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
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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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Complete APTX deletion in a patient with ataxia with oculomotor apraxia type 1. | van Minkelen R | BMC medical genetics | 2015 | PMID: 26285866 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=APTX | - | - | - | - |
Text-mined citations for rs144076460 ...
HelpRecord last updated Apr 15, 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.