NM_017849.4(TMEM127):c.556G>C (p.Ala186Pro) AND Hereditary pheochromocytoma-paraganglioma

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 16, 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:: RCV000700721.7

Allele description [Variation Report for NM_017849.4(TMEM127):c.556G>C (p.Ala186Pro)]

NM_017849.4(TMEM127):c.556G>C (p.Ala186Pro)

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.556G>C (p.Ala186Pro)

HGVS:

NC_000002.12:g.96253969C>G
NG_027695.1:g.17045G>C
NM_001193304.3:c.556G>C
NM_017849.4:c.556G>CMANE SELECT
NP_001180233.1:p.Ala186Pro
NP_060319.1:p.Ala186Pro
NP_060319.1:p.Ala186Pro
LRG_528t1:c.556G>C
LRG_528:g.17045G>C
LRG_528p1:p.Ala186Pro
NC_000002.11:g.96919707C>G
NM_017849.3:c.556G>C

Protein change:

A186P

Links:

dbSNP: rs764012422

NCBI 1000 Genomes Browser:

rs764012422

Molecular consequence:

NM_001193304.3:c.556G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_017849.4:c.556G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

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SRP347441 (322)
SRA
sphingosine 1-phosphate receptor 3 [Homo sapiens]
sphingosine 1-phosphate receptor 3 [Homo sapiens]
gi|2079618405|ref|NP_001382777.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000829489	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 16, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30877234, 33051659, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000829489

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 16, 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

Targeted next-generation sequencing detects rare genetic events in pheochromocytoma and paraganglioma.

Ben Aim L, Pigny P, Castro-Vega LJ, Buffet A, Amar L, Bertherat J, Drui D, Guilhem I, Baudin E, Lussey-Lepoutre C, Corsini C, Chabrier G, Briet C, Faivre L, Cardot-Bauters C, Favier J, Gimenez-Roqueplo AP, Burnichon N.

J Med Genet. 2019 Aug;56(8):513-520. doi: 10.1136/jmedgenet-2018-105714. Epub 2019 Mar 15.

PubMed [citation]

PMID:: 30877234

Genotype-Phenotype Features of Germline Variants of the TMEM127 Pheochromocytoma Susceptibility Gene: A 10-Year Update.

Armaiz-Pena G, Flores SK, Cheng ZM, Zhang X, Esquivel E, Poullard N, Vaidyanathan A, Liu Q, Michalek J, Santillan-Gomez AA, Liss M, Ahmadi S, Katselnik D, Maldonado E, Salgado SA, Jimenez C, Fishbein L, Hamidi O, Else T, Lechan R, Tischler AS, Benn DE, et al.

J Clin Endocrinol Metab. 2021 Jan 1;106(1):e350-e364. doi: 10.1210/clinem/dgaa741.

PubMed [citation]

PMID:: 33051659
PMCID:: PMC7765648

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000829489.4

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

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: 577865). This missense change has been observed in individual(s) with pheochromocytoma (PMID: 30877234, 33051659). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 186 of the TMEM127 protein (p.Ala186Pro).

#	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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