NM_018105.3(THAP1):c.25G>A (p.Gly9Ser) AND Torsion dystonia 6

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 16, 2018
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000853344.1

Allele description [Variation Report for NM_018105.3(THAP1):c.25G>A (p.Gly9Ser)]

NM_018105.3(THAP1):c.25G>A (p.Gly9Ser)

Gene:

THAP1:THAP domain containing 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8p11.21

Genomic location:

Preferred name:

NM_018105.3(THAP1):c.25G>A (p.Gly9Ser)

HGVS:

NC_000008.11:g.42843070C>T
NG_011837.1:g.5262G>A
NM_018105.3:c.25G>AMANE SELECT
NM_199003.2:c.25G>A
NP_060575.1:p.Gly9Ser
NP_945354.1:p.Gly9Ser
NC_000008.10:g.42698213C>T
NM_018105.2:c.25G>A

Protein change:

G9S

Links:

dbSNP: rs267607112

NCBI 1000 Genomes Browser:

rs267607112

Molecular consequence:

NM_018105.3:c.25G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_199003.2:c.25G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Torsion dystonia 6 (DYT6)
Synonyms:: DYT-THAP1
Identifiers:: MONDO: MONDO:0011264; MedGen: C1414216; Orphanet: 98806; OMIM: 602629

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000996206	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 16, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000996206

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Oct 16, 2018)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV000996206.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (1)

Description

This variant has not been previously reported or functionally characterized in the literature to our knowledge. However, a different missense variant involving the same amino acid position (p.Gly9Cys) has been reported as a heterozygous change in a patient with limb, cervical, and masticatory dystonia (PMID: 20083799). Additionally, functional studies suggest that the p.Gly9Cys variant results in a reduction in the DNA-binding affinity of the THAP1-encoded protein (PMID: 22844099). The c.25G>A (p.Gly9Ser) variant detected in this individual is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. Based on the available evidence, the c.25G>A (p.Gly9Ser) variant is classified as likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: May 16, 2025

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