NM_005060.4(RORC):c.1456T>A (p.Phe486Ile) AND Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 10, 2018
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:: RCV000793258.6

Allele description [Variation Report for NM_005060.4(RORC):c.1456T>A (p.Phe486Ile)]

NM_005060.4(RORC):c.1456T>A (p.Phe486Ile)

Gene:

RORC:RAR related orphan receptor C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q21.3

Genomic location:

Preferred name:

NM_005060.4(RORC):c.1456T>A (p.Phe486Ile)

HGVS:

NC_000001.11:g.151807573A>T
NG_029118.1:g.29300T>A
NM_001001523.2:c.1393T>A
NM_005060.4:c.1456T>AMANE SELECT
NP_001001523.1:p.Phe465Ile
NP_005051.2:p.Phe486Ile
LRG_1322t1:c.1456T>A
LRG_1322t2:c.1393T>A
LRG_1322:g.29300T>A
LRG_1322p1:p.Phe486Ile
LRG_1322p2:p.Phe465Ile
NC_000001.10:g.151780049A>T
NM_005060.3:c.1456T>A

Protein change:

F465I

Links:

dbSNP: rs1572032352

NCBI 1000 Genomes Browser:

rs1572032352

Molecular consequence:

NM_001001523.2:c.1393T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005060.4:c.1456T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency
Synonyms:: Immunodeficiency 42
Identifiers:: MONDO: MONDO:0014710; MedGen: C5567647; OMIM: 616622

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000932604	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 10, 2018)	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

SCV000932604

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 10, 2018)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000932604.4

#	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 phenylalanine with isoleucine at codon 486 of the RORC protein (p.Phe486Ile). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and isoleucine. This variant is not present in population databases (ExAC no frequency). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with RORC-related disease.

#	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: Feb 20, 2024

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