NM_017849.4(TMEM127):c.652G>A (p.Glu218Lys) AND Hereditary pheochromocytoma-paraganglioma

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 20, 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:: RCV000797795.11

Allele description

NM_017849.4(TMEM127):c.652G>A (p.Glu218Lys)

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.652G>A (p.Glu218Lys)

HGVS:

NC_000002.12:g.96253873C>T
NG_027695.1:g.17141G>A
NM_001193304.3:c.652G>A
NM_017849.4:c.652G>AMANE SELECT
NP_001180233.1:p.Glu218Lys
NP_060319.1:p.Glu218Lys
NP_060319.1:p.Glu218Lys
LRG_528t1:c.652G>A
LRG_528:g.17141G>A
LRG_528p1:p.Glu218Lys
NC_000002.11:g.96919611C>T
NM_017849.3:c.652G>A

Protein change:

E218K

Links:

dbSNP: rs746291260

NCBI 1000 Genomes Browser:

rs746291260

Molecular consequence:

NM_001193304.3:c.652G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_017849.4:c.652G>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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Fulvia fulva strain Race 4 chromosome 1, whole genome shotgun sequence
Fulvia fulva strain Race 4 chromosome 1, whole genome shotgun sequence
gi|2647580579|gb|CM069375.1||gnl|WG JJH|chr1

Nucleotide
Acacia torta (0)
Structure
USP6 N-terminal-like protein isoform X1 [Rattus norvegicus]
USP6 N-terminal-like protein isoform X1 [Rattus norvegicus]
gi|564392149|ref|XP_006254294.1|

Protein
Fulvia fulva ECP4 protein (Ecp4) gene, complete cds.
Fulvia fulva ECP4 protein (Ecp4) gene, complete cds.
PopSet: 1715031067

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000937374	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 20, 2023)	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

SCV000937374

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 20, 2023)

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, SCV000937374.7

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

Description

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 218 of the TMEM127 protein (p.Glu218Lys). This variant is present in population databases (rs746291260, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with TMEM127-related conditions. ClinVar contains an entry for this variant (Variation ID: 643972). 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 tolerated. 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.

#	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: Jun 23, 2024

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