NM_017849.4(TMEM127):c.469C>T (p.Gln157Ter) AND Hereditary pheochromocytoma-paraganglioma

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 18, 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:: RCV000536742.8

Allele description [Variation Report for NM_017849.4(TMEM127):c.469C>T (p.Gln157Ter)]

NM_017849.4(TMEM127):c.469C>T (p.Gln157Ter)

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.469C>T (p.Gln157Ter)

HGVS:

NC_000002.12:g.96254056G>A
NG_027695.1:g.16958C>T
NM_001193304.3:c.469C>T
NM_017849.4:c.469C>TMANE SELECT
NP_001180233.1:p.Gln157Ter
NP_060319.1:p.Gln157Ter
NP_060319.1:p.Gln157Ter
LRG_528t1:c.469C>T
LRG_528:g.16958C>T
LRG_528p1:p.Gln157Ter
NC_000002.11:g.96919794G>A
NM_017849.3:c.469C>T

Protein change:

Q157*

Links:

dbSNP: rs780133289

NCBI 1000 Genomes Browser:

rs780133289

Molecular consequence:

NM_001193304.3:c.469C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_017849.4:c.469C>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
SCV000637925	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 18, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22419703, 20154675, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000637925

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 18, 2023)

germline

clinical testing

PubMed (3)
[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

TMEM127 screening in a large cohort of patients with pheochromocytoma and/or paraganglioma.

Abermil N, Guillaud-Bataille M, Burnichon N, Venisse A, Manivet P, Guignat L, Drui D, Chupin M, Josseaume C, Affres H, Plouin PF, Bertherat J, Jeunemaître X, Gimenez-Roqueplo AP.

J Clin Endocrinol Metab. 2012 May;97(5):E805-9. doi: 10.1210/jc.2011-3360. Epub 2012 Mar 14.

PubMed [citation]

PMID:: 22419703

Germline mutations in TMEM127 confer susceptibility to pheochromocytoma.

Qin Y, Yao L, King EE, Buddavarapu K, Lenci RE, Chocron ES, Lechleiter JD, Sass M, Aronin N, Schiavi F, Boaretto F, Opocher G, Toledo RA, Toledo SP, Stiles C, Aguiar RC, Dahia PL.

Nat Genet. 2010 Mar;42(3):229-33. doi: 10.1038/ng.533. Epub 2010 Feb 14.

PubMed [citation]

PMID:: 20154675
PMCID:: PMC2998199

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000637925.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Gln157*) in the TMEM127 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 82 amino acid(s) of the TMEM127 protein. This variant is present in population databases (rs780133289, gnomAD 0.002%). This premature translational stop signal has been observed in individuals with pheochromocytoma (PMID: 22419703; Invitae). ClinVar contains an entry for this variant (Variation ID: 463849). This variant disrupts a region of the TMEM127 protein in which other variant(s) (p.Gln159*) have been determined to be pathogenic (PMID: 20154675; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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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