U.S. flag

An official website of the United States government

NM_007315.4(STAT1):c.1765G>T (p.Ala589Ser) AND multiple conditions

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
May 1, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000678288.10

Allele description

NM_007315.4(STAT1):c.1765G>T (p.Ala589Ser)

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.1765G>T (p.Ala589Ser)
HGVS:
  • NC_000002.12:g.190978964C>A
  • NG_008294.1:g.40287G>T
  • NM_001384880.1:c.1705G>T
  • NM_001384881.1:c.1771G>T
  • NM_001384882.1:c.1759G>T
  • NM_001384883.1:c.1666G>T
  • NM_001384884.1:c.1771G>T
  • NM_001384885.1:c.1606G>T
  • NM_001384886.1:c.1765G>T
  • NM_001384887.1:c.1672G>T
  • NM_001384888.1:c.1735G>T
  • NM_001384889.1:c.1765G>T
  • NM_001384890.1:c.1675G>T
  • NM_001384891.1:c.1801G>T
  • NM_007315.4:c.1765G>TMANE SELECT
  • NM_139266.3:c.1765G>T
  • NP_001371809.1:p.Ala569Ser
  • NP_001371810.1:p.Ala591Ser
  • NP_001371811.1:p.Ala587Ser
  • NP_001371812.1:p.Ala556Ser
  • NP_001371813.1:p.Ala591Ser
  • NP_001371814.1:p.Ala536Ser
  • NP_001371815.1:p.Ala589Ser
  • NP_001371816.1:p.Ala558Ser
  • NP_001371817.1:p.Ala579Ser
  • NP_001371818.1:p.Ala589Ser
  • NP_001371819.1:p.Ala559Ser
  • NP_001371820.1:p.Ala601Ser
  • NP_009330.1:p.Ala589Ser
  • NP_009330.1:p.Ala589Ser
  • NP_644671.1:p.Ala589Ser
  • LRG_111t1:c.1765G>T
  • LRG_111:g.40287G>T
  • LRG_111p1:p.Ala589Ser
  • NC_000002.11:g.191843690C>A
  • NM_007315.3:c.1765G>T
Protein change:
A536S
Links:
dbSNP: rs745491762
NCBI 1000 Genomes Browser:
rs745491762
Molecular consequence:
  • NM_001384880.1:c.1705G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384881.1:c.1771G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384882.1:c.1759G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384883.1:c.1666G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384884.1:c.1771G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384885.1:c.1606G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384886.1:c.1765G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384887.1:c.1672G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384888.1:c.1735G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384889.1:c.1765G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384890.1:c.1675G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384891.1:c.1801G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007315.4:c.1765G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_139266.3:c.1765G>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000804345Geisinger Autism and Developmental Medicine Institute, Geisinger Health System
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Feb 20, 2018) 		unknownprovider interpretation, clinical testing

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

SCV001232985Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(May 1, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknown1not providednot provided1not providedclinical testing, provider interpretation
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

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 Geisinger Autism and Developmental Medicine Institute, Geisinger Health System, SCV000804345.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedprovider interpretation PubMed (1)
2not provided1not providednot providedclinical testing PubMed (1)

Description

This 8 year old male has a history of autism spectrum disorder, myoclonic jerks, coordination disorder, ADHD, disruptive behavior, tachycardia, joint laxity, recurrent rashes, recurrent respiratory illness, and eosinophilic esophagitis. Genetic testing to date, including exome sequencing, has not yielded a diagnosis. The p.Ala589Ser variant in STAT1 is present in the gnomAD African population at a frequency of 0.025%. Computational prediction models are inconsistent. Subsequent clinical testing showed normal neutrophil function studies and quantitative immunoglobulins.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided
2unknownunknown1not providednot provided1not providednot providednot provided

From Invitae, SCV001232985.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 424473). This variant has not been reported in the literature in individuals affected with STAT1-related conditions. This variant is present in population databases (rs745491762, gnomAD 0.02%). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 589 of the STAT1 protein (p.Ala589Ser).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 11, 2024