SF3A1

protein-coding

splicing factor 3a subunit 1, the group of SF3a complex|U2 small nuclear ribonucleoprotein

Gene summary

This gene encodes a subunit of the splicing factor 3a protein complex. The splicing factor 3a heterotrimer is a component of the mature U2 small nuclear ribonucleoprotein particle (snRNP). U2 small nuclear ribonucleoproteins play a critical role in spliceosome assembly and pre-mRNA splicing. [provided by RefSeq, Aug 2014]

MANE transcript

NM_005877.6

Inheritance

—

ClinVar variants

P:1U:53B:1

Top phenotype

Malignant lymphoma, large B-cell, diffuse

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr22:30,331,988-30,356,919

External References & Databases

Ensembl (ENSG00000099995)

Transcript & Mutation Effects

hg38 • Region Span ~24.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SF3A1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 48

not providedTotal: 2

Malignant lymphoma, large B-cell, diffuseTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005877.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	1 clinvar		2
missense			52 clinvar			52
nonsense						0
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)						0
Total	1	0	53	1	0	55

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005877.6	RefSeq	NP_005868.1	16	MANE Select
ENST00000215793.13	Ensembl	ENSP00000215793.7	16	MANE Select
ENST00000411423.1	Ensembl	ENSP00000412715.1	3	Standard
ENST00000444440.1	Ensembl	ENSP00000400862.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Spliceosome - Homo sapiens (human)
mRNA Processing
Metabolism of RNA
mRNA Splicing - Major Pathway
mRNA Splicing

Biological Process

mRNA 3'-splice site recognition
mRNA splicing, via spliceosome
mRNA processing

Molecular Function

RNA binding
protein binding

Cellular Component

nucleoplasm
spliceosomal complex
U2-type spliceosomal complex
U2 snRNP
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000215793
Coding exons: 16
Length: 24960
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125748
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	4.16	203	452	0.449	0.0000256	5176
Missense (PolyPhen)		81	244.05	0.3319		2745
Synonymous	-0.293	177	172	1.03	0.0000102	1540
Loss of Function	4.96	6	39.7	0.151	0.00000205	451

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000030	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000057	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000063	0.000062	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Subunit of the splicing factor SF3A 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. May also be involved in the assembly of the 'E' complex.;

Recessive Scores

pRec: 0.121

Intolerance Scores

LoFtool: 0.210
RVIS EVS: -0.78
RVIS percentile EVS: 12.77

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.729

Gene Damage Prediction

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