NM_007315.4(STAT1):c.467T>C (p.Ile156Thr) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 19, 2022
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:: RCV003780993.1

Allele description [Variation Report for NM_007315.4(STAT1):c.467T>C (p.Ile156Thr)]

NM_007315.4(STAT1):c.467T>C (p.Ile156Thr)

Gene:

STAT1:signal transducer and activator of transcription 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q32.2

Genomic location:

Preferred name:

NM_007315.4(STAT1):c.467T>C (p.Ile156Thr)

HGVS:

NC_000002.12:g.190999700A>G
NG_008294.1:g.19551T>C
NM_001384880.1:c.467T>C
NM_001384881.1:c.473T>C
NM_001384882.1:c.467T>C
NM_001384883.1:c.463-3T>C
NM_001384884.1:c.473T>C
NM_001384885.1:c.467T>C
NM_001384886.1:c.467T>C
NM_001384887.1:c.467T>C
NM_001384888.1:c.467T>C
NM_001384889.1:c.467T>C
NM_001384890.1:c.377T>C
NM_001384891.1:c.503T>C
NM_007315.4:c.467T>CMANE SELECT
NM_139266.3:c.467T>C
NP_001371809.1:p.Ile156Thr
NP_001371810.1:p.Ile158Thr
NP_001371811.1:p.Ile156Thr
NP_001371813.1:p.Ile158Thr
NP_001371814.1:p.Ile156Thr
NP_001371815.1:p.Ile156Thr
NP_001371816.1:p.Ile156Thr
NP_001371817.1:p.Ile156Thr
NP_001371818.1:p.Ile156Thr
NP_001371819.1:p.Ile126Thr
NP_001371820.1:p.Ile168Thr
NP_009330.1:p.Ile156Thr
NP_009330.1:p.Ile156Thr
NP_644671.1:p.Ile156Thr
LRG_111t1:c.467T>C
LRG_111:g.19551T>C
LRG_111p1:p.Ile156Thr
NC_000002.11:g.191864426A>G
NM_007315.3:c.467T>C

Protein change:

I126T

Molecular consequence:

NM_001384883.1:c.463-3T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001384880.1:c.467T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001384881.1:c.473T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001384882.1:c.467T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001384884.1:c.473T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001384885.1:c.467T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001384886.1:c.467T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001384887.1:c.467T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001384888.1:c.467T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001384889.1:c.467T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001384890.1:c.377T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001384891.1:c.503T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_007315.4:c.467T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_139266.3:c.467T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Immunodeficiency 31B
Synonyms:: STAT1 DEFICIENCY, AUTOSOMAL RECESSIVE; Mycobacterial and viral infections, susceptibility to, autosomal recessive; IMMUNODEFICIENCY 31B, MYCOBACTERIAL AND VIRAL INFECTIONS, AUTOSOMAL RECESSIVE
Identifiers:: MONDO: MONDO:0013427; MedGen: C3151088; OMIM: 613796

Name:: Autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome
Synonyms:: Candidiasis, familial, 7; Immunodeficiency 31C
Identifiers:: MONDO: MONDO:0013599; MedGen: C3279990; Orphanet: 391487; OMIM: 614162

Name:: Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency
Synonyms:: IMMUNODEFICIENCY 31A, MYCOBACTERIOSIS, AUTOSOMAL DOMINANT; STAT1 DEFICIENCY, AUTOSOMAL DOMINANT; Immunodeficiency 31a
Identifiers:: MONDO: MONDO:0013956; MedGen: C4013950; Orphanet: 319595; OMIM: 614892

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004569768	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 19, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23403048, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004569768

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 19, 2022)

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

Gain-of-function STAT1 mutations are associated with PD-L1 overexpression and a defect in B-cell survival.

Romberg N, Morbach H, Lawrence MG, Kim S, Kang I, Holland SM, Milner JD, Meffre E.

J Allergy Clin Immunol. 2013 Jun;131(6):1691-3. doi: 10.1016/j.jaci.2013.01.004. Epub 2013 Feb 10. No abstract available. Erratum in: J Allergy Clin Immunol. 2013 Dec;132(6):1460.

PubMed [citation]

PMID:: 23403048
PMCID:: PMC3672340

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, SCV004569768.1

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

Description

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. Experimental studies have shown that this missense change affects STAT1 function (PMID: 23403048). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This missense change has been observed in individual(s) with clinical features of STAT1-related conditions (PMID: 23403048). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 156 of the STAT1 protein (p.Ile156Thr).

#	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: Mar 5, 2024

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