STAG3

stromal antigen 3, the group of Armadillo like helical domain containing|Cohesin complex

Basic information

Region (hg38): 7:100177563-100214387

Links

ENSG00000066923 ∙ NCBI:10734 ∙ OMIM:608489 ∙ HGNC:11356 ∙ Uniprot:Q9UJ98 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spermatogenic failure 61 (Limited), mode of inheritance: AR
• premature ovarian failure 8 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Premature ovarian failure 8	AR	Obstetric	Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency	Endocrine; Genitourinary; Obstetric	22428046; 24597867; 26059840; 31125047; 31682730; 32634216
One described individual was reported as additionally affected by ovarian cancer

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STAG3 gene.

• Premature ovarian failure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STAG3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				11	2	13
missense		1	61	7	2	71
nonsense	1	4				5
start loss						0
frameshift		3				3
inframe indel		1				1
splice donor/acceptor (+/-2bp)		3				3
splice region				1	1	2
non coding				1	30	31
Total	1	12	61	19	34

Highest pathogenic variant AF is 0.00000658

Variants in STAG3

This is a list of pathogenic ClinVar variants found in the STAG3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-100180396-G-C			Benign (May 16, 2021)
7-100180567-C-T		Inborn genetic diseases	Uncertain significance (Dec 01, 2023)
7-100180604-G-T		Spermatogenic failure 61 • Premature ovarian failure 8	Benign (Jul 15, 2021)
7-100180615-C-T		Inborn genetic diseases	Uncertain significance (Jan 24, 2023)
7-100180624-C-T		Inborn genetic diseases	Uncertain significance (Feb 17, 2022)
7-100180660-A-G		Inborn genetic diseases	Uncertain significance (Jul 21, 2021)
7-100180662-A-C		Premature ovarian failure 8 • Spermatogenic failure 61	Benign (Jul 15, 2021)
7-100180694-T-C			Benign (May 26, 2021)
7-100180880-G-GT			Benign (May 24, 2021)
7-100181901-C-A			Benign (Jun 03, 2021)
7-100181901-C-CAA			Benign (Jun 04, 2021)
7-100182145-C-A		Inborn genetic diseases	Uncertain significance (Nov 30, 2021)
7-100182263-G-A			Benign (May 16, 2021)
7-100182659-C-G			Benign (May 16, 2021)
7-100182660-G-A			Benign (May 16, 2021)
7-100182751-G-C		Inborn genetic diseases	Uncertain significance (Nov 13, 2023)
7-100182760-A-G		Inborn genetic diseases	Likely benign (Jan 30, 2024)
7-100182792-G-GC		Premature ovarian failure 8	Pathogenic (Dec 23, 2021)
7-100183032-T-C			Benign (May 16, 2021)
7-100186091-G-T			Benign (May 16, 2021)
7-100186198-A-C			Likely pathogenic (Aug 18, 2017)
7-100186209-G-C		Inborn genetic diseases	Uncertain significance (Feb 23, 2023)
7-100186275-A-G		Inborn genetic diseases	Uncertain significance (Nov 01, 2022)
7-100186287-G-A		Inborn genetic diseases	Uncertain significance (Jul 12, 2022)
7-100188861-TC-T		Premature ovarian failure 8	Pathogenic (Mar 06, 2014)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STAG3	protein_coding	protein_coding	ENST00000426455	33	43926

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.72e-13	1.00	125614	0	134	125748	0.000533

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.66	569	692	0.823	0.0000403	8033
Missense in Polyphen		123	177.26	0.69388		2040
Synonymous	1.08	253	276	0.917	0.0000159	2388
Loss of Function	4.32	33	72.8	0.453	0.00000379	819

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00102	0.00102
Ashkenazi Jewish	0.00	0.00
East Asian	0.000326	0.000326
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000642	0.000642
Middle Eastern	0.000326	0.000326
South Asian	0.000758	0.000752
Other	0.000978	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Meiosis specific component of cohesin complex. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The meiosis- specific cohesin complex probably replaces mitosis specific cohesin complex when it dissociates from chromatin during prophase I. {ECO:0000250|UniProtKB:O70576}.
• Disease: DISEASE: Premature ovarian failure 8 (POF8) [MIM:615723]: An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol. {ECO:0000269|PubMed:24597867, ECO:0000303|PubMed:22428046}. Note=The disease is caused by mutations affecting the gene represented in this entry. A homozygous deletion in STAG3 predicted to result in frameshift and premature truncation, has been shown to be the cause of premature ovarian failure in a large consanguineous family. {ECO:0000269|PubMed:24597867}.
• Pathway: Oocyte meiosis - Homo sapiens (human);Reproduction;Meiotic synapsis;Meiosis;Cell Cycle (Consensus)

Recessive Scores

• pRec: 0.116

Intolerance Scores

• loftool: 0.921
• rvis_EVS: -1.1
• rvis_percentile_EVS: 6.91

Haploinsufficiency Scores

• pHI: 0.106
• hipred: Y
• hipred_score: 0.683
• ghis: 0.525

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.680

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Stag3
• Phenotype: skeleton phenotype; reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: sister chromatid cohesion;synaptonemal complex assembly
• Cellular component: chromosome, centromeric region;chromatin;synaptonemal complex;extracellular space;nucleus;cohesin complex;meiotic cohesin complex
• Molecular function: chromatin binding