Genetic Information

Gene & Transcript Details

Gene
SF3B1
Transcript
NM_012433.2 MANE Select
Total Exons
—
Reference Sequence
NC_000002.11
Alternative Transcripts
IDStatusDetails
NM_012433.2 Alternative 4314 nt | 49–3963
NM_012433.3 RefSeq Select 4338 nt | 95–4009
NM_012433.4 MANE Select 6463 nt | 30–3944

Variant Details

HGVS Notation
NM_012433.2:c.1866G>T
Protein Change
E622D
Location
Exon 14 (Exon 14 of )
14
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers
—

Clinical & Population Data

Population Frequency

gnomAD
Global Frequency
0.0 in 100,000
Extremely Rare
ACMG Criteria Applied PM2
This variant is absent or extremely rare in population databases (PM2 criteria applies).

ClinVar

Open
Classification
Unknown
0 publications
Clinical Statement

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COSMIC Somatic Evidence

Open
COSMIC ID
COSM110693
Recurrence
43 occurrences
PM1 Criteria
Applied
COSMIC Database Preview
COSMIC Preview
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Functional Impact & Domains

Functional Domain

Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain.
Related Variants in This Domain
No evidence of other pathogenic variants at this position in gene SF3B1.

Functional Studies & Therapeutic Relevance

Functional Summary

Error in OpenAI Consolidation. OncoKB: SF3B1E622DSF3B1E622DSomaticNCBI Gene:23451|Show additional gene information Variant OverviewSF3B1, a component of the spliceosome complex, is frequently mutated in hematologic malignancies.The SF3B1 E622D mutation is likely oncogenic.Hide mutation effect description The SF3B1 E622D mutation occurs in the HEAT domain, which functions as a scaffolding region for protein interactions. This mutation results in abnormal recruitment of splicing machinery to pre-mRNA, thus leading to aberrant splicing of target transcripts (PMID: 25428262, 21909114). Gene expression and splicing profiling of CD34+ cells from patients with myelodysplastic syndrome (MDS) harboring this mutation demonstrated that mutant SF3B1 predominantly affects genes involved in myelodysplastic syndrome pathogenesis, iron homeostasis, mitochondrial metabolism and RNA splicing/processing (PMID: 25428262). JAX-CKB: No results found

Database Previews
OncoKB
OncoKB Preview
JAX-CKB
JAX-CKB Preview

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Computational Analysis

Pathogenicity Predictions

SpliceAI
Predictor Consensus
Mixed/VUS
PP3 Applied
No
REVEL Score
0.0
Threshold: ≥0.75 = PP3 applied

SpliceAI Scores

Window: ±500bp
Effect Type Score Position
- Acceptor Loss (AL) 0.02 -254 bp
- Donor Loss (DL) 0.27 1 bp
+ Acceptor Gain (AG) 0.0 292 bp
+ Donor Gain (DG) 0.03 -3 bp
High impact (≥0.5) Medium impact (0.2-0.49) Low impact (<0.2)

VCEP Guidelines

Applied ACMG/AMP Criteria (VCEP Specific)

Filter Criteria:
PS3

PS3 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

PM2

PM2 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)