NM_152296.5(ATP1A3):c.665_666delinsTG (p.Thr222Met) AND Dystonia 12

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 22, 2023
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:: RCV002001830.5

Allele description [Variation Report for NM_152296.5(ATP1A3):c.665_666delinsTG (p.Thr222Met)]

NM_152296.5(ATP1A3):c.665_666delinsTG (p.Thr222Met)

Gene:

ATP1A3:ATPase Na+/K+ transporting subunit alpha 3 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

19q13.2

Genomic location:

Preferred name:

NM_152296.5(ATP1A3):c.665_666delinsTG (p.Thr222Met)

HGVS:

NC_000019.10:g.41985364_41985365delinsCA
NG_008015.1:g.13866_13867delinsTG
NM_001256213.2:c.698_699delinsTG
NM_001256214.2:c.704_705delinsTG
NM_152296.5:c.665_666delinsTGMANE SELECT
NP_001243142.1:p.Thr233Met
NP_001243143.1:p.Thr235Met
NP_689509.1:p.Thr222Met
LRG_1186t1:c.665_666delinsTG
LRG_1186:g.13866_13867delinsTG
LRG_1186p1:p.Thr222Met
NC_000019.9:g.42489516_42489517delinsCA

Protein change:

T222M

Links:

dbSNP: rs2145978673

NCBI 1000 Genomes Browser:

rs2145978673

Molecular consequence:

NM_001256213.2:c.698_699delinsTG - missense variant - [Sequence Ontology: SO:0001583]
NM_001256214.2:c.704_705delinsTG - missense variant - [Sequence Ontology: SO:0001583]
NM_152296.5:c.665_666delinsTG - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Dystonia 12 (DYT12)
Synonyms:: DYT-ATP1A3; Rapid-Onset Dystonia-Parkinsonism
Identifiers:: MONDO: MONDO:0007496; MedGen: C1868681; Orphanet: 71517; OMIM: 128235

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002214892	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 22, 2023)	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

SCV002214892

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 22, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002214892.4

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

Description

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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1435421). This variant has not been reported in the literature in individuals affected with ATP1A3-related conditions. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 222 of the ATP1A3 protein (p.Thr222Met).

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

Last Updated: Sep 29, 2024

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