NM_017849.4(TMEM127):c.556G>C (p.Ala186Pro) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 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:: RCV002343526.3

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 cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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SRP347096 (33)
SRA
Anthoptilum sp. g YK-2023
Anthoptilum sp. g YK-2023
Anthoptilum sp. g YK-2023 Genome sequencing and assembly

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Component(Core) Links for Nucleotide (Select 1694459891) (3)
Nucleotide
Taxonomy Links for Nucleotide (Select 1238387720) (1)
Taxonomy
Taxonomy Links for Protein (Select 617303122) (1)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002650915	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 16, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30877234, 33051659 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002650915

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 16, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

Details of each submission

From Ambry Genetics, SCV002650915.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.A186P variant (also known as c.556G>C), located in coding exon 3 of the TMEM127 gene, results from a G to C substitution at nucleotide position 556. The alanine at codon 186 is replaced by proline, an amino acid with highly similar properties. This alteration has been identified in multiple individuals diagnosed with pheochromocytoma (Ben Aim L et al. J Med Genet, 2019 Aug;56:513-520; Armaiz-Pena G et al. J Clin Endocrinol Metab, 2021 Jan;106:e350-e364). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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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