SF3B1

splicing factor 3b subunit 1, the group of B-WICH chromatin-remodelling complex subunits|SF3b complex|Armadillo like helical domain containing

Basic information

Region (hg38): 2:197388515-197435079

Links

ENSG00000115524 ∙ NCBI:23451 ∙ OMIM:605590 ∙ HGNC:10768 ∙ Uniprot:O75533 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SF3B1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SF3B1 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			1	6	10	17
missense		2	9			11
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2	2	4
non coding						0
Total	0	2	11	6	10

Variants in SF3B1

This is a list of pathogenic ClinVar variants found in the SF3B1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-197392312-A-G			Benign (Jul 27, 2018)
2-197392351-G-A			Benign (Dec 31, 2019)
2-197393071-T-C		SF3B1-related disorder	Benign (Apr 05, 2019)
2-197393196-G-A			Benign (Dec 31, 2019)
2-197398016-T-C		SF3B1-related disorder	Uncertain significance (Sep 20, 2022)
2-197398035-A-G			Benign/Likely benign (Aug 01, 2024)
2-197398499-T-C		SF3B1-related disorder	Likely benign (Oct 28, 2019)
2-197400047-T-C		SF3B1-related disorder	Likely benign (Mar 22, 2019)
2-197400137-T-C		SF3B1-related disorder	Likely benign (Apr 25, 2019)
2-197400802-A-G		SF3B1-related disorder	Benign (Nov 01, 2019)
2-197400846-G-A		not specified	Uncertain significance (Aug 05, 2024)
2-197401887-C-T		B-cell chronic lymphocytic leukemia • Papillary renal cell carcinoma type 1	Likely pathogenic (May 31, 2016)
2-197402097-A-C			Uncertain significance (Jul 01, 2017)
2-197402101-T-G		Neurodevelopmental disorder	Uncertain significance (Jun 19, 2024)
2-197402104-G-T			Benign (Dec 31, 2019)
2-197402108-T-A		Acute myeloid leukemia	Likely pathogenic (Oct 02, 2014)
2-197402108-T-G		Acute myeloid leukemia	Likely pathogenic (Oct 02, 2014)
2-197402109-T-A		Acute myeloid leukemia	Likely pathogenic (Oct 02, 2014)
2-197402109-T-C		Acute myeloid leukemia	Likely pathogenic (Oct 02, 2014)
2-197402109-T-G		Acute myeloid leukemia	Likely pathogenic (Oct 02, 2014)
2-197402110-T-A		Acute myeloid leukemia	Likely pathogenic (Oct 02, 2014)
2-197402110-T-C		Acute myeloid leukemia • Chronic myelogenous leukemia, BCR-ABL1 positive • SF3B1-related disorder	Conflicting classifications of pathogenicity (Dec 08, 2022)
2-197402110-T-G		Acute myeloid leukemia	Likely pathogenic (Oct 02, 2014)
2-197402138-A-T		SF3B1-related disorder	Likely benign (Apr 25, 2019)
2-197402635-C-A		Myelodysplastic syndrome progressed to acute myeloid leukemia • Acute myeloid leukemia • Myelodysplastic syndrome	Pathogenic/Likely pathogenic (Oct 10, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SF3B1	protein_coding	protein_coding	ENST00000335508	25	45308

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.79e-11	125697	0	2	125699	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	7.70	141	724	0.195	0.0000379	8501
Missense in Polyphen		22	241.67	0.091031		2804
Synonymous	0.280	232	237	0.977	0.0000121	2539
Loss of Function	7.76	1	72.1	0.0139	0.00000424	823

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000179	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex (PubMed:27720643). SF3B complex is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Sequence independent binding of SF3A/SF3B complex upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA (PubMed:12234937). May also be involved in the assembly of the 'E' complex (PubMed:10882114). Belongs also to the minor U12-dependent spliceosome, which is involved in the splicing of rare class of nuclear pre-mRNA intron (PubMed:15146077). {ECO:0000269|PubMed:10882114, ECO:0000269|PubMed:12234937, ECO:0000269|PubMed:15146077, ECO:0000269|PubMed:27720643}.
• Pathway: Spliceosome - Homo sapiens (human);mRNA Processing;B-WICH complex positively regulates rRNA expression;Positive epigenetic regulation of rRNA expression;Epigenetic regulation of gene expression;Gene expression (Transcription);Metabolism of RNA;mRNA Splicing - Major Pathway;mRNA Splicing - Minor Pathway;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

• pRec: 0.230

Intolerance Scores

• rvis_EVS: -1.13
• rvis_percentile_EVS: 6.43

Haploinsufficiency Scores

• pHI: 0.996
• hipred: Y
• hipred_score: 0.859
• ghis: 0.689

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.963

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sf3b1
• Phenotype: homeostasis/metabolism phenotype; skeleton phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); immune system phenotype

Zebrafish Information Network

• Gene name: sf3b1
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: RNA splicing, via transesterification reactions;mRNA splicing, via spliceosome;positive regulation of gene expression, epigenetic
• Cellular component: nucleus;nucleoplasm;spliceosomal complex;U2 snRNP;U12-type spliceosomal complex;nuclear speck;U11/U12 snRNP;U2-type prespliceosome;U2-type precatalytic spliceosome;catalytic step 2 spliceosome
• Molecular function: RNA binding;mRNA binding;protein binding