NM_017831.4(RNF125):c.488C>T (p.Ser163Leu) AND Tenorio syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 2, 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:: RCV000162242.12

Allele description [Variation Report for NM_017831.4(RNF125):c.488C>T (p.Ser163Leu)]

NM_017831.4(RNF125):c.488C>T (p.Ser163Leu)

Gene:

RNF125:ring finger protein 125 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_017831.4(RNF125):c.488C>T (p.Ser163Leu)

HGVS:

NC_000018.10:g.32045716C>T
NG_042056.1:g.32235C>T
NM_017831.4:c.488C>TMANE SELECT
NP_060301.2:p.Ser163Leu
NC_000018.9:g.29625679C>T
NM_017831.3:c.488C>T
Q96EQ8:p.Ser163Leu

Protein change:

S163L; SER163LEU

Links:

UniProtKB: Q96EQ8#VAR_073354; OMIM: 610432.0002; dbSNP: rs373764886

NCBI 1000 Genomes Browser:

rs373764886

Molecular consequence:

NM_017831.4:c.488C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Tenorio syndrome (TNORS)
Synonyms:: OVERGROWTH, MACROCEPHALY, AND INTELLECTUAL DISABILITY SYNDROME
Identifiers:: MONDO: MONDO:0014553; MedGen: C4015710; OMIM: 616260

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000212233	OMIM	no assertion criteria provided	Pathogenic (Dec 1, 2014)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000821319	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 2, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25196541, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000212233

OMIM

no assertion criteria provided

Pathogenic
(Dec 1, 2014)

germline

literature only

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

SCV000821319

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 2, 2021)

germline

clinical testing

PubMed (2)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A new overgrowth syndrome is due to mutations in RNF125.

Tenorio J, Mansilla A, Valencia M, Martínez-Glez V, Romanelli V, Arias P, Castrejón N, Poletta F, Guillén-Navarro E, Gordo G, Mansilla E, García-Santiago F, González-Casado I, Vallespín E, Palomares M, Mori MA, Santos-Simarro F, García-Miñaur S, Fernández L, Mena R, Benito-Sanz S, del Pozo Á, et al.

Hum Mutat. 2014 Dec;35(12):1436-41. doi: 10.1002/humu.22689.

PubMed [citation]

PMID:: 25196541

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, SCV000212233.3

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

Description

In a 19-year-old Spanish man with an overgrowth, macrocephaly, and impaired intellectual development syndrome (TNORS; 616260), Tenorio et al. (2014) identified a de novo heterozygous c.488C-T transition in the RNF125 gene, resulting in a ser163-to-leu (S163L) substitution. The mutation was not found in 600 chromosomes from healthy Spanish controls or in 350 exomes from Spanish controls. It was not present in the 1000 Genomes Project database, but it was found in 1 (0.0077%) of 13,005 chromosomes in the Exome Variant Server database. The patient also had several episodes of Raynaud phenomena, dry conjunctivitis, and recurrent aphthous stomatitis.

#	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, SCV000821319.3

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

Description

This sequence change replaces serine with leucine at codon 163 of the RNF125 protein (p.Ser163Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs373764886, ExAC 0.006%). This missense change has been observed in individual(s) with overgrowth syndrome (PMID: 25196541). ClinVar contains an entry for this variant (Variation ID: 183421). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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: Sep 29, 2024

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