NM_017849.4(TMEM127):c.475C>T (p.Gln159Ter) AND Hereditary pheochromocytoma-paraganglioma

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 6, 2020
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:: RCV001381352.5

Allele description [Variation Report for NM_017849.4(TMEM127):c.475C>T (p.Gln159Ter)]

NM_017849.4(TMEM127):c.475C>T (p.Gln159Ter)

Gene:

TMEM127:transmembrane protein 127 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q11.2

Genomic location:

Preferred name:

NM_017849.4(TMEM127):c.475C>T (p.Gln159Ter)

HGVS:

NC_000002.12:g.96254050G>A
NG_027695.1:g.16964C>T
NM_001193304.3:c.475C>T
NM_017849.4:c.475C>TMANE SELECT
NP_001180233.1:p.Gln159Ter
NP_060319.1:p.Gln159Ter
NP_060319.1:p.Gln159Ter
LRG_528t1:c.475C>T
LRG_528:g.16964C>T
LRG_528p1:p.Gln159Ter
NC_000002.11:g.96919788G>A
NM_017849.3:c.475C>T
p.Q159*

Protein change:

Q159*; GLN159TER

Links:

OMIM: 613403.0002; dbSNP: rs121908830

NCBI 1000 Genomes Browser:

rs121908830

Molecular consequence:

NM_001193304.3:c.475C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_017849.4:c.475C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary pheochromocytoma-paraganglioma
Synonyms:: Hereditary Paraganglioma-Pheochromocytoma Syndromes; Hereditary Paragangliomas and Pheochromocytomas
Identifiers:: MONDO: MONDO:0017366; MedGen: C1708353

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001579708	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 6, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 28855235, 28384794, 20154675, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001579708

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 6, 2020)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

Molecular and phenotypic evaluation of a novel germline TMEM127 mutation with an uncommon clinical presentation.

Deng Y, Flores SK, Cheng Z, Qin Y, Schwartz RC, Malchoff C, Dahia PLM.

Endocr Relat Cancer. 2017 Nov;24(11):L79-L82. doi: 10.1530/ERC-17-0359. Epub 2017 Aug 30. No abstract available. Erratum in: Endocr Relat Cancer. 2018 Sep;25(9):X3. doi: 10.1530/ERC-17-0359e.

PubMed [citation]

PMID:: 28855235
PMCID:: PMC5741081

Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention.

Bausch B, Schiavi F, Ni Y, Welander J, Patocs A, Ngeow J, Wellner U, Malinoc A, Taschin E, Barbon G, Lanza V, Söderkvist P, Stenman A, Larsson C, Svahn F, Chen JL, Marquard J, Fraenkel M, Walter MA, Peczkowska M, Prejbisz A, Jarzab B, et al.

JAMA Oncol. 2017 Sep 1;3(9):1204-1212. doi: 10.1001/jamaoncol.2017.0223.

PubMed [citation]

PMID:: 28384794
PMCID:: PMC5824290

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001579708.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the TMEM127 protein. Other variant(s) that disrupt this region (p.Tyr178Leufs*48) have been determined to be pathogenic (PMID: 28855235, 28384794). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has been observed in individual(s) with paraganglioma-pheochromocytoma syndrome (PMID: 20154675). ClinVar contains an entry for this variant (Variation ID: 108). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the TMEM127 gene (p.Gln159*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 80 amino acids of the TMEM127 protein.

#	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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