NM_000176.3(NR3C1):c.256A>G (p.Met86Val) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 13, 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:: RCV003553776.2

Allele description [Variation Report for NM_000176.3(NR3C1):c.256A>G (p.Met86Val)]

NM_000176.3(NR3C1):c.256A>G (p.Met86Val)

Genes:

LOC129994918:ATAC-STARR-seq lymphoblastoid active region 23342 [Gene]
NR3C1:nuclear receptor subfamily 3 group C member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q31.3

Genomic location:

Preferred name:

NM_000176.3(NR3C1):c.256A>G (p.Met86Val)

HGVS:

NC_000005.10:g.143400584T>C
NG_009062.1:g.39929A>G
NG_174364.1:g.142T>C
NM_000176.3:c.256A>GMANE SELECT
NM_001018074.1:c.256A>G
NM_001018075.1:c.256A>G
NM_001018076.2:c.256A>G
NM_001018077.1:c.256A>G
NM_001020825.2:c.256A>G
NM_001024094.2:c.256A>G
NM_001204258.2:c.178A>G
NM_001204259.2:c.1A>G
NM_001204260.2:c.-12A>G
NM_001204261.2:c.-36A>G
NM_001204262.2:c.-690A>G
NM_001204263.2:c.-735A>G
NM_001204264.2:c.-750A>G
NM_001204265.2:c.256A>G
NM_001364180.2:c.256A>G
NM_001364181.2:c.256A>G
NM_001364182.1:c.256A>G
NM_001364183.2:c.256A>G
NM_001364184.2:c.256A>G
NM_001364185.1:c.256A>G
NP_000167.1:p.Met86Val
NP_001018084.1:p.Met86Val
NP_001018085.1:p.Met86Val
NP_001018086.1:p.Met86Val
NP_001018087.1:p.Met86Val
NP_001018661.1:p.Met86Val
NP_001019265.1:p.Met86Val
NP_001191187.1:p.Met60Val
NP_001191188.1:p.Met1Val
NP_001191194.1:p.Met86Val
NP_001351109.1:p.Met86Val
NP_001351110.1:p.Met86Val
NP_001351111.1:p.Met86Val
NP_001351112.1:p.Met86Val
NP_001351113.1:p.Met86Val
NP_001351114.1:p.Met86Val
NC_000005.9:g.142780149T>C

Protein change:

M1V

Molecular consequence:

NM_001204260.2:c.-12A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001204261.2:c.-36A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001204262.2:c.-690A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001204263.2:c.-735A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001204264.2:c.-750A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001204259.2:c.1A>G - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_000176.3:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001018074.1:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001018075.1:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001018076.2:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001018077.1:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001020825.2:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001024094.2:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001204258.2:c.178A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001204259.2:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001204265.2:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001364180.2:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001364181.2:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001364182.1:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001364183.2:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001364184.2:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001364185.1:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004275540	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 13, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31008420, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004275540

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 13, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Functional Characterization of Glucocorticoid Receptor Variants Is Required to Avoid Misinterpretation of NGS Data.

Foussier L, Vitellius G, Bouligand J, Amazit L, Bouvattier C, Young J, Trabado S, Lombès M.

J Endocr Soc. 2019 May 1;3(5):865-881. doi: 10.1210/js.2019-00028.

PubMed [citation]

PMID:: 31008420
PMCID:: PMC6467410

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004275540.1

#	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 methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 86 of the NR3C1 protein (p.Met86Val). This variant is present in population databases (rs772735144, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with NR3C1-related conditions. 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 disruptive. Experimental studies have shown that this missense change does not substantially affect NR3C1 function (PMID: 31008420). 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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