NM_017849.4(TMEM127):c.554G>A (p.Gly185Glu) AND Hereditary pheochromocytoma-paraganglioma

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 15, 2022
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:: RCV002923973.2

Allele description

NM_017849.4(TMEM127):c.554G>A (p.Gly185Glu)

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.554G>A (p.Gly185Glu)

HGVS:

NC_000002.12:g.96253971C>T
NG_027695.1:g.17043G>A
NM_001193304.3:c.554G>A
NM_001407282.1:c.302G>A
NM_001407283.1:c.302G>A
NM_017849.4:c.554G>AMANE SELECT
NP_001180233.1:p.Gly185Glu
NP_001394211.1:p.Gly101Glu
NP_001394212.1:p.Gly101Glu
NP_060319.1:p.Gly185Glu
NP_060319.1:p.Gly185Glu
LRG_528t1:c.554G>A
LRG_528:g.17043G>A
LRG_528p1:p.Gly185Glu
NC_000002.11:g.96919709C>T
NM_017849.3:c.554G>A

Protein change:

G101E

Molecular consequence:

NM_001193304.3:c.554G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407282.1:c.302G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407283.1:c.302G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_017849.4:c.554G>A - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003276061	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 15, 2022)	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

SCV003276061

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 15, 2022)

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	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 Invitae, SCV003276061.2

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

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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with TMEM127-related conditions. This variant is present in population databases (rs774413835, gnomAD 0.003%). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 185 of the TMEM127 protein (p.Gly185Glu).

#	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: Aug 11, 2024

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