AFF3

ALF transcription elongation factor 3, the group of AF4/FMR2 family|Super elongation complex

Basic information

Region (hg38): 2:99545418-100192428

Previous symbols: [ "LAF4" ]

Links

ENSG00000144218 ∙ NCBI:3899 ∙ OMIM:601464 ∙ HGNC:6473 ∙ Uniprot:P51826 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• KINSSHIP syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
KINSSHIP syndrome	AD	General	Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency	Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Pulmonary; Renal	31388108; 33961779

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AFF3 gene.

• Inborn genetic diseases (44 variants)
• not provided (40 variants)
• KINSSHIP syndrome (9 variants)
• AFF3-related condition (6 variants)
• - (2 variants)
• See cases (2 variants)
• not specified (1 variants)
• AFF3-related neurodevelopmental disorders (1 variants)
• AFF3-associated disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AFF3 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				16	3	19
missense	2	3	59	3	1	68
nonsense						0
start loss						0
frameshift		1	1			2
inframe indel			2			2
splice donor/acceptor (+/-2bp)			1			1
splice region			1	2		3
non coding			2	2		4
Total	2	4	65	21	4

Variants in AFF3

This is a list of pathogenic ClinVar variants found in the AFF3 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-99554326-C-T		not specified	Uncertain significance (Dec 08, 2022)
2-99554354-G-A		AFF3-related disorder	Likely benign (Jan 02, 2020)
2-99554396-C-T		AFF3-related disorder	Likely benign (Aug 01, 2022)
2-99554430-A-T		Inborn genetic diseases	Uncertain significance (Jan 27, 2022)
2-99554455-C-T		Inborn genetic diseases	Likely benign (Apr 13, 2023)
2-99554482-C-T		Inborn genetic diseases	Uncertain significance (Jun 22, 2023)
2-99554503-T-G		Inborn genetic diseases	Uncertain significance (Nov 22, 2023)
2-99554513-G-GGGGGAT			Uncertain significance (Jan 10, 2022)
2-99554521-G-C		Inborn genetic diseases	Uncertain significance (Oct 02, 2023)
2-99554696-C-G		Inborn genetic diseases	Uncertain significance (Aug 28, 2023)
2-99554731-T-C			Uncertain significance (Oct 28, 2022)
2-99558914-G-C			Uncertain significance (Mar 30, 2022)
2-99560401-T-C		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
2-99560429-T-C		Inborn genetic diseases	Uncertain significance (Dec 13, 2023)
2-99565539-T-C			Uncertain significance (Aug 01, 2023)
2-99565547-T-C		-	no classification for the single variant (-)
2-99568869-G-A			Uncertain significance (Apr 20, 2021)
2-99578335-G-A		AFF3-related disorder	Benign (Mar 13, 2019)
2-99578384-G-C			Benign (Mar 01, 2024)
2-99578389-C-T			Likely benign (Dec 01, 2022)
2-99578406-G-C		Inborn genetic diseases	Uncertain significance (Aug 17, 2021)
2-99578434-ATTG-A		AFF3-related disorder	Uncertain significance (Aug 26, 2023)
2-99582812-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 31, 2024)
2-99582825-C-T		AFF3-related disorder	Benign (Feb 08, 2024)
2-99582924-G-C		AFF3-related disorder	Uncertain significance (Mar 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AFF3	protein_coding	protein_coding	ENST00000356421	23	596879

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000418	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.71	607	738	0.823	0.0000441	8221
Missense in Polyphen		136	210.11	0.64728		2511
Synonymous	0.228	312	317	0.984	0.0000226	2437
Loss of Function	6.30	7	59.4	0.118	0.00000311	693

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000182	0.0000176
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Putative transcription activator that may function in lymphoid development and oncogenesis. Binds, in vitro, to double- stranded DNA.

Recessive Scores

• pRec: 0.126

Intolerance Scores

• loftool: 0.441
• rvis_EVS: -1.46
• rvis_percentile_EVS: 3.89

Haploinsufficiency Scores

• pHI: 0.811
• hipred: Y
• hipred_score: 0.520
• ghis: 0.558

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.892

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Aff3
• Phenotype: hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); craniofacial phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: regulation of transcription, DNA-templated;response to tumor necrosis factor;embryonic hindlimb morphogenesis
• Cellular component: nucleus;nucleoplasm;cytosol;transcription elongation factor complex;nuclear body;ELL-EAF complex
• Molecular function: double-stranded DNA binding;DNA-binding transcription factor activity