Genetic Information

Gene & Transcript Details

Gene
FH
Transcript
NM_000143.4 MANE Select
Total Exons
—
Reference Sequence
NC_000001.10
Alternative Transcripts
IDStatusDetails
NM_000143.3 RefSeq Select 1877 nt | 64–1596
NM_000143.2 Alternative 1791 nt | 33–1565
NM_000143.4 MANE Select 1791 nt | 34–1566

Variant Details

HGVS Notation
NM_000143.4:c.143del
Protein Change
N48Ifs*5
Location
Exon 2 (Exon 2 of )
2
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

""

COSMIC Somatic Evidence

Open
COSMIC ID
Recurrence
0 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 FH.

Functional Studies & Therapeutic Relevance

Functional Summary

Error in OpenAI Consolidation. OncoKB: FHN48Ifs*5FHN48Ifs*5SomaticNCBI Gene:2271|Show additional gene information Variant OverviewFH, an enzyme that converts fumarate to malate in the TCA cycle, is infrequently altered in cancer.The FH N48Ifs*5 is a truncating mutation in a tumor suppressor gene, and therefore is likely oncogenic.Hide mutation effect description The mutation effect description for truncating mutations in FH is: FH truncating mutations can produce several forms of C-terminally truncated proteins. These mutations have been found as germline mutations in leiomyomatosis and renal cell cancer (PMID: 11865300, 15937070, 12772087, 12761039). Endogenous expression of these mutations in cutaneous leiomyomata samples demonstrated that they are inactivating as measured by reduced protein activity compared to normal skin samples (PMID: 11865300). JAX-CKB: No results found

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

Click on previews to view full database entries. External databases may require institutional access.

Computational Analysis

Pathogenicity Predictions

SpliceAI
Predictor Consensus
Unknown
PP3 Applied
No
REVEL Score
0.0
Threshold: ≥0.75 = PP3 applied

SpliceAI Scores

Window: ±500bp
Effect Type Score Position
- Acceptor Loss (AL) 0.0 31 bp
- Donor Loss (DL) 0.0 134 bp
+ Acceptor Gain (AG) 0.0 -356 bp
+ Donor Gain (DG) 0.0 -103 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:
PVS1

PVS1 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

PS3

PS3 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

PM2

PM2 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)