Genetic Information
Gene & Transcript Details
Gene
MLH3
Transcript
NM_001040108.2
MANE Select
Total Exons
—
Reference Sequence
NC_000014.8
Alternative Transcripts
| ID | Status | Details |
|---|---|---|
| NM_001040108.2 | MANE Select | 7820 nt | 152–4513 |
| NM_001040108.1 | RefSeq Select | 7911 nt | 217–4578 |
Variant Details
HGVS Notation
NM_001040108.2:c.3488G>A
Protein Change
G1163D
Location
Exon 5
(Exon 5 of )
5
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers
—
Clinical & Population Data
Population Frequency
gnomAD Global Frequency
0.213 in 100,000
Extremely Rare
ACMG Criteria Applied
None
ClinVar
OpenClassification
Uncertain Significance (VUS)
2 publications
Clinical Statement
"This variant has been reported in ClinVar as Uncertain significance (2 clinical laboratories) and as Benign (6 clinical laboratories)."
COSMIC Somatic Evidence
OpenCOSMIC ID
COSM9995595
Recurrence
2 occurrences
PM1 Criteria
Not Applied
COSMIC Database Preview
Accessing full COSMIC database details requires institutional login or subscription.
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 MLH3.
Functional Summary
Error in OpenAI Consolidation. OncoKB: MLH3G1163DMLH3G1163DSomaticNCBI Gene:27030|Show additional gene information Variant OverviewMLH3, a DNA mismatch repair protein, is infrequently altered in cancer.The MLH3 G1163D mutation has not specifically been reviewed by the OncoKB team, and therefore its biological significance is unknown. JAX-CKB: No results found
Database Previews
OncoKB
JAX-CKB
Click on previews to view full database entries. External databases may require institutional access.
Computational Analysis
Pathogenicity Predictions
SpliceAIPredictor 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) | 0.0 | 449 bp |
| Donor Loss (DL) | 0.0 | 22 bp |
| Acceptor Gain (AG) | 0.11 | 22 bp |
| Donor Gain (DG) | 0.02 | -82 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:
BP4
BP4 (Unknown (Pre-LLM))
From pre-LLM assessment (LLM Failed)