NM_018475.5(TMEM165):c.376C>T (p.Arg126Cys) AND TMEM165-congenital disorder of glycosylation

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 31, 2021
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:: RCV000029181.8

Allele description [Variation Report for NM_018475.5(TMEM165):c.376C>T (p.Arg126Cys)]

NM_018475.5(TMEM165):c.376C>T (p.Arg126Cys)

Gene:

TMEM165:transmembrane protein 165 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q12

Genomic location:

Preferred name:

NM_018475.5(TMEM165):c.376C>T (p.Arg126Cys)

HGVS:

NC_000004.12:g.55411782C>T
NG_032881.1:g.20870C>T
NM_018475.5:c.376C>TMANE SELECT
NP_060945.2:p.Arg126Cys
NC_000004.11:g.56277949C>T
NM_018475.4:c.376C>T
NR_073070.2:n.712C>T
Q9HC07:p.Arg126Cys

Protein change:

R126C; ARG126CYS

Links:

UniProtKB: Q9HC07#VAR_068446; OMIM: 614726.0003; dbSNP: rs387907222

NCBI 1000 Genomes Browser:

rs387907222

Molecular consequence:

NM_018475.5:c.376C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_073070.2:n.712C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: TMEM165-congenital disorder of glycosylation
Synonyms:: CDG IIk; Congenital disorder of glycosylation type 2k; TMEM165-CDG
Identifiers:: MONDO: MONDO:0013870; MedGen: C3553571; Orphanet: 314667; OMIM: 614727

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Acanthophyllum sarawschanicum voucher LE 01042363 internal transcribed spacer 1 ...
Acanthophyllum sarawschanicum voucher LE 01042363 internal transcribed spacer 1 and 5.8S ribosomal RNA gene, complete sequence; and internal transcribed spacer 2, partial sequence
gi|1722693271|gb|MN310912.1|

Nucleotide
PF3D7_1130300 [Plasmodium falciparum 3D7]
PF3D7_1130300 [Plasmodium falciparum 3D7]
Gene ID:36312532

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000051826	OMIM	no assertion criteria provided	Pathogenic (Jul 13, 2012)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000958962	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 31, 2021)	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

SCV000051826

OMIM

no assertion criteria provided

Pathogenic
(Jul 13, 2012)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV000958962

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 31, 2021)

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
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

TMEM165 deficiency causes a congenital disorder of glycosylation.

Foulquier F, Amyere M, Jaeken J, Zeevaert R, Schollen E, Race V, Bammens R, Morelle W, Rosnoblet C, Legrand D, Demaegd D, Buist N, Cheillan D, Guffon N, Morsomme P, Annaert W, Freeze HH, Van Schaftingen E, Vikkula M, Matthijs G.

Am J Hum Genet. 2012 Jul 13;91(1):15-26. doi: 10.1016/j.ajhg.2012.05.002. Epub 2012 Jun 7.

PubMed [citation]

PMID:: 22683087
PMCID:: PMC3397274

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 OMIM, SCV000051826.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In an American girl with congenital disorder of glycosylation type 2k (CDG2K; 614727), Foulquier et al. (2012) identified compound heterozygosity for 2 mutations in the TMEM165 gene: a 376C-T transition resulting in an arg126-to-cys (R126C) substitution, and a 910G-A transition resulting in a gly304-to-arg (G304R; 614726.0004) substitution. Both affected residues are highly conserved. The patient had short stature, facial dysmorphism, wrinkled skin, abnormal fat distribution, dysplastic toenails, amelogenesis imperfecta, and multiple skeletal anomalies. Patient fibroblasts showed decreased immunostaining for TMEM165 compared to control.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000958962.2

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

#	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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