ClinVar Genomic variation as it relates to human health
NM_018105.3(THAP1):c.427A>G (p.Met143Val)
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
-
NM_018105.3(THAP1):c.427A>G (p.Met143Val)
Variation ID: 225489 Accession: VCV000225489.7
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 8p11.21 8: 42838177 (GRCh38) [ NCBI UCSC ] 8: 42693320 (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 Dec 6, 2016 Feb 20, 2024 Feb 22, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_018105.3:c.427A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_060575.1:p.Met143Val missense NM_199003.2:c.*69A>G 3 prime UTR NC_000008.11:g.42838177T>C NC_000008.10:g.42693320T>C NG_011837.1:g.10155A>G Q9NVV9:p.Met143Val - Protein change
- M143V
- Other names
- -
- Canonical SPDI
- NC_000008.11:42838176:T:C
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- Unknown function
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00005
The Genome Aggregation Database (gnomAD) 0.00006
Exome Aggregation Consortium (ExAC) 0.00007
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
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. |
|||
THAP1 | - | - |
GRCh38 GRCh37 |
176 | 233 |
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. |
---|---|---|---|---|
Uncertain significance (1) |
criteria provided, single submitter
|
Jul 21, 2016 | RCV000302642.4 | |
Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
|
Feb 22, 2023 | RCV000490517.4 |
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. |
|
---|---|---|---|---|---|
Uncertain significance
(Mar 18, 2016)
|
criteria provided, single submitter
Method: reference population
|
Torsion dystonia 6
Affected status: unknown
Allele origin:
germline
|
Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center
Accession: SCV000267526.1
First in ClinVar: May 25, 2017 Last updated: May 25, 2017 |
Number of individuals with the variant: 1
Age: 40-69 years
Ethnicity/Population group: East Asian
Geographic origin: South Korean
|
|
Uncertain significance
(Jul 21, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000343497.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Number of individuals with the variant: 1
Sex: mixed
|
|
Uncertain significance
(Dec 31, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Torsion dystonia 6
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV001135003.1
First in ClinVar: Mar 16, 2020 Last updated: Mar 16, 2020 |
Comment:
A heterozygous missense variation in exon 3 of the THAP1 gene that results in the amino acid substitution of Valine for Methionine at codon 143 … (more)
A heterozygous missense variation in exon 3 of the THAP1 gene that results in the amino acid substitution of Valine for Methionine at codon 143 was detected. The observed variant c.427A>G (p.Met143Val) has not been reported in the 1000 genomes database and has a minor allele frequency of 0.007% in the ExAC database. The in silico prediction of the variant is damaging by LRT. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as variant of unknown significance. (less)
Clinical Features:
Unilateral facial palsy (present)
Age: 0-9 years
Sex: female
Ethnicity/Population group: Indian Hindu
Geographic origin: India
Method: DNA was used to perform targeted gene capture using a custom capture kit. Libraries were sequenced to mean >80-100X coverage on Illumina sequencing platform. Sequence obtained were aligned to human references genome using BWA program and analyzed using Picard and GATK-Lite toolkit to identify variants in the targeted genes relevant to clinical indication.
|
|
Uncertain significance
(Feb 22, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Torsion dystonia 6
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV003254286.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
This missense change has been observed in individual(s) with dystonia (PMID: 20669277, 27913194). ClinVar contains an entry for this variant (Variation ID: 225489). Algorithms developed … (more)
This missense change has been observed in individual(s) with dystonia (PMID: 20669277, 27913194). ClinVar contains an entry for this variant (Variation ID: 225489). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant is present in population databases (rs374512193, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 143 of the THAP1 protein (p.Met143Val). (less)
|
Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
---|---|---|---|---|
Unknown function
|
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV001135003.1
|
|
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Genetic screening of THAP1 in primary dystonia patients of India. | Giri S | Neuroscience letters | 2017 | PMID: 27913194 |
THAP1 mutations and dystonia phenotypes: genotype phenotype correlations. | Xiromerisiou G | Movement disorders : official journal of the Movement Disorder Society | 2012 | PMID: 22903657 |
Prevalence of THAP1 sequence variants in German patients with primary dystonia. | Söhn AS | Movement disorders : official journal of the Movement Disorder Society | 2010 | PMID: 20669277 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=THAP1 | - | - | - | - |
Text-mined citations for rs374512193 ...
HelpRecord last updated Feb 28, 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.