NM_021830.5(TWNK):c.404G>A (p.Gly135Glu) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 4, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000994493.25

Allele description [Variation Report for NM_021830.5(TWNK):c.404G>A (p.Gly135Glu)]

NM_021830.5(TWNK):c.404G>A (p.Gly135Glu)

Gene:

TWNK:twinkle mtDNA helicase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q24.31

Genomic location:

Preferred name:

NM_021830.5(TWNK):c.404G>A (p.Gly135Glu)

HGVS:

NC_000010.11:g.100988614G>A
NG_011646.1:g.3902C>T
NG_012624.1:g.6079G>A
NM_001163812.2:c.404G>A
NM_001163813.2:c.-120+1001G>A
NM_001163814.2:c.-120+1001G>A
NM_001368275.1:c.-58+1001G>A
NM_021830.5:c.404G>AMANE SELECT
NP_001157284.1:p.Gly135Glu
NP_068602.2:p.Gly135Glu
NC_000010.10:g.102748371G>A
NC_000010.10:g.102748371G>A
NR_160738.1:n.1072G>A
NR_160740.1:n.1072G>A
NR_160741.1:n.1072G>A
NR_160742.1:n.1072G>A

Protein change:

G135E

Links:

dbSNP: rs375005531

NCBI 1000 Genomes Browser:

rs375005531

Molecular consequence:

NM_001163813.2:c.-120+1001G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001163814.2:c.-120+1001G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001368275.1:c.-58+1001G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001163812.2:c.404G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_021830.5:c.404G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_160738.1:n.1072G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160740.1:n.1072G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160741.1:n.1072G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160742.1:n.1072G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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sugar transport protein MST4-like [Cucumis melo]
sugar transport protein MST4-like [Cucumis melo]
gi|2316548789|ref|XP_008465176.2|

Protein
RecName: Full=Benzene 1,2-dioxygenase subunit alpha; AltName: Full=Benzene 1,2-d...
RecName: Full=Benzene 1,2-dioxygenase subunit alpha; AltName: Full=Benzene 1,2-dioxygenase P1 subunit; AltName: Full=Toluene 2,3-dioxygenase subunit alpha
gi|166225908|sp|P0C618.1|BNZA_PSEPU

Protein
Lymphoma, Primary Cutaneous Anaplastic Large Cell
Lymphoma, Primary Cutaneous Anaplastic Large Cell
Anaplastic lymphoma of the skin which develops as a primary neoplasm expressing the CD30 ANTIGEN. It is characterized by solitary nodules or ulcerated tumors....<br/>Year introduced: 2008

MeSH

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001148065	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Jun 1, 2016)	germline	clinical testing	Citation Link,
SCV002933157	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 4, 2024)	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

SCV001148065

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Uncertain significance
(Jun 1, 2016)

germline

clinical testing

Citation Link,

SCV002933157

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 4, 2024)

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	not provided	not provided	clinical testing
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 CeGaT Center for Human Genetics Tuebingen, SCV001148065.27

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

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002933157.2

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

Description

This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 135 of the TWNK protein (p.Gly135Glu). This variant is present in population databases (rs375005531, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with TWNK-related conditions. ClinVar contains an entry for this variant (Variation ID: 806558). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TWNK protein function with a negative predictive value of 95%. 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.

#	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: Oct 20, 2024

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