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.1876A>G
Protein Change
N626D
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
0.000398 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
COSM131555
Recurrence
12 occurrences
PM1 Criteria
Not Applied
COSMIC Database 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: SF3B1N626DSF3B1N626DSomaticNCBI Gene:23451|Show additional gene information Variant OverviewSF3B1, a component of the spliceosome complex, is frequently mutated in hematologic malignancies.There is no available functional data about the SF3B1 N626D mutation (last reviewed on 02/02/2023). However, it has been identified as a statistically significant hotspot and is likely to be oncogenic. 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
Pathogenic
PP3 Applied
Yes
REVEL Score
0.0
Threshold: ≥0.75 = PP3 applied

SpliceAI Scores

Window: ±500bp
Effect Type Score Position
- Acceptor Loss (AL) 0.02 -244 bp
- Donor Loss (DL) 0.08 11 bp
+ Acceptor Gain (AG) 0.0 69 bp
+ Donor Gain (DG) 0.04 -114 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)

PP3

PP3 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)