cancervariants / cancervariants/variation-normalization
Unable to normalize HIST1H3B K28M
- Dominant language
- Python
- Stars
- 15
- Forks
- 2
- PR merge metrics
- No merged PRs in 30d
Description
### Describe the bug
Apologies for such a specific ticket.
The variation normalizer is unable to normalize this variant: HIST1H3B K28M (gnomad vcf: 6-26031978-T-A)
https://normalize.cancervariants.org/variation/normalize?q=HIST1H3B%20K28M
### Steps to reproduce
https://normalize.cancervariants.org/variation/normalize?q=HIST1H3B%20K28M
### Expected behavior
I would expect this variant to be able to be normalized because it is a SNV that leads to a simple protein consequence change (so it should be supported)
### Current behavior
it says unable to normalize :(
### Possible reason(s)
I have a hunch that this may be related to the fact that this gene has a LOT of aliases:
```
{
"query": "HIST1H3B",
"warnings": [],
"match_type": 80,
"service_meta_": {
"name": "gene-normalizer",
"version": "0.11.0",
"response_datetime": "2026-03-25 16:35:53.619126+00:00",
"url": "https://github.com/cancervariants/gene-normalization"
},
"gene": {
"id": "normalize.gene.hgnc:4776",
"extensions": [
{
"name": "aliases",
"value": [
"HIST1H3B",
"H3C1",
"H3C10",
"H3FL",
"H3C12",
"H3C8",
"H3C4",
"H3C3",
"H3C6",
"H3/l",
"H3C11",
"H3C7"
]
},
```
a very similar gene () also has some of the same aliases but is considered a different gene from the normalizer (and has a different hgnc id)
```
{
"query": "HIST1H3H",
"warnings": [],
"match_type": 80,
"service_meta_": {
"name": "gene-normalizer",
"version": "0.11.0",
"response_datetime": "2026-03-25 16:38:56.266681+00:00",
"url": "https://github.com/cancervariants/gene-normalization"
},
"gene": {
"id": "normalize.gene.hgnc:4775",
"extensions": [
{
"name": "aliases",
"value": [
"H3FK",
"H3/k",
"H3C1",
"H3C12",
"H3C2",
"H3C8",
"H3C4",
"HIST1H3H",
"H3C3",
"H3C6",
"H3F1K",
"H3C11",
"H3C7"
]
},
```
I actually wonder if the root issue here is in the gene normalizer after looking at the above output (maybe these should be the same concept?)...
but also when trying to normalize HIST1H3B K28M, I get this output in the variation normalizer:
```
api-1 | INFO: 172.19.0.1:61338 - "GET /variation/normalize?q=HIST1H3B%20K37M&hgvs_dup_del_mode=default HTTP/1.1" 200 OK
api-1 | Accession, ENSP00000484841, not found in SeqRepo
api-1 | Accession, ENSP00000484841.2, not found in SeqRepo
api-1 | INFO: 172.19.0.1:61338 - "GET /variation/normalize?q=HIST1H3B%20K37M&hgvs_dup_del_mode=default HTTP/1.1" 200 OK
api-1 | Accession, ENSP00000358160, not found in SeqRepo
api-1 | Accession, ENSP00000358160, not found in SeqRepo
```
### Suggested fix
_No response_
### Branch, commit, and/or version
any (but I have been using prod which is 0.15.4)
### Screenshots
_No response_
### Environment details
not applicable here
### Additional details
_No response_
### Contribution
None
Contributor guide
No contributing guide indexed for this repository
Research direction
Start by reproducing HIST1H3B K28M through the /variation/normalize endpoint and compare the result with the expected SNV normalization. Trace the gene-normalizer resolution and the SeqRepo lookups for the reported ENSP accessions; done means the variant returns a normalized result rather than being rejected.
Written by the indexing model from the issue text.
Assessment
- Tech stack
- python
- Domain
- api, backend
- Issue type
- Bug
- Difficulty
- 4/5
- Estimated time
- 3-5 days
- Activity status
- Quiet
- Clarity
- Needs clarification
- Newbie friendliness
- 45/100