NM_139276.3(STAT3):c.454C>T (p.Arg152Trp) AND multiple conditions

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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 11, 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:: RCV000653281.9

Allele description

NM_139276.3(STAT3):c.454C>T (p.Arg152Trp)

Gene:

STAT3:signal transducer and activator of transcription 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.2

Genomic location:

Preferred name:

NM_139276.3(STAT3):c.454C>T (p.Arg152Trp)

HGVS:

NC_000017.11:g.42339328G>A
NG_007370.1:g.54168C>T
NM_001369512.1:c.454C>T
NM_001369513.1:c.454C>T
NM_001369514.1:c.454C>T
NM_001369516.1:c.454C>T
NM_001369517.1:c.454C>T
NM_001369518.1:c.454C>T
NM_001369519.1:c.454C>T
NM_001369520.1:c.454C>T
NM_001384984.1:c.454C>T
NM_001384985.1:c.376C>T
NM_001384986.1:c.454C>T
NM_001384987.1:c.454C>T
NM_001384988.1:c.454C>T
NM_001384989.1:c.373-516C>T
NM_001384990.1:c.454C>T
NM_001384991.1:c.454C>T
NM_001384992.1:c.454C>T
NM_001384993.1:c.454C>T
NM_003150.4:c.454C>T
NM_139276.3:c.454C>TMANE SELECT
NM_213662.2:c.454C>T
NP_001356441.1:p.Arg152Trp
NP_001356442.1:p.Arg152Trp
NP_001356443.1:p.Arg152Trp
NP_001356445.1:p.Arg152Trp
NP_001356446.1:p.Arg152Trp
NP_001356447.1:p.Arg152Trp
NP_001356448.1:p.Arg152Trp
NP_001356449.1:p.Arg152Trp
NP_001371913.1:p.Arg152Trp
NP_001371914.1:p.Arg126Trp
NP_001371915.1:p.Arg152Trp
NP_001371916.1:p.Arg152Trp
NP_001371917.1:p.Arg152Trp
NP_001371919.1:p.Arg152Trp
NP_001371920.1:p.Arg152Trp
NP_001371921.1:p.Arg152Trp
NP_001371922.1:p.Arg152Trp
NP_003141.2:p.Arg152Trp
NP_644805.1:p.Arg152Trp
NP_644805.1:p.Arg152Trp
NP_998827.1:p.Arg152Trp
LRG_112t1:c.454C>T
LRG_112:g.54168C>T
LRG_112p1:p.Arg152Trp
NC_000017.10:g.40491346G>A
NM_139276.2:c.454C>T

Protein change:

R126W

Links:

dbSNP: rs869312890

NCBI 1000 Genomes Browser:

rs869312890

Molecular consequence:

NM_001384989.1:c.373-516C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001369512.1:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369513.1:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369514.1:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369516.1:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369517.1:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369518.1:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369519.1:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369520.1:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001384984.1:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001384985.1:c.376C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001384986.1:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001384987.1:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001384988.1:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001384990.1:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001384991.1:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001384992.1:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001384993.1:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003150.4:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_139276.3:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_213662.2:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hyper-IgE recurrent infection syndrome 1, autosomal dominant
Synonyms:: Hyperimmunoglobulin E recurrent infection syndrome, autosomal dominant; HIES autosomal dominant; AD hyperimmunoglobulin E syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007818; MedGen: CN031130; Orphanet: 2314; OMIM: 147060

Name:: STAT3 gain of function
Identifiers:: MedGen: C4288261

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000775160	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 11, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25359994, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000775160

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 11, 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

Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations.

Milner JD, Vogel TP, Forbes L, Ma CA, Stray-Pedersen A, Niemela JE, Lyons JJ, Engelhardt KR, Zhang Y, Topcagic N, Roberson ED, Matthews H, Verbsky JW, Dasu T, Vargas-Hernandez A, Varghese N, McClain KL, Karam LB, Nahmod K, Makedonas G, Mace EM, Sorte HS, et al.

Blood. 2015 Jan 22;125(4):591-9. doi: 10.1182/blood-2014-09-602763. Epub 2014 Oct 30.

PubMed [citation]

PMID:: 25359994
PMCID:: PMC4304103

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, SCV000775160.6

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

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 152 of the STAT3 protein (p.Arg152Trp). This missense change has been observed in individual(s) with multi-organ autoimmune disease (PMID: 25359994). In at least one individual the variant was observed to be de novo. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects STAT3 function (PMID: 25359994). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt STAT3 protein function. ClinVar contains an entry for this variant (Variation ID: 224846).

#	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

ClinVar

Relating variation to medicine