cancervariants / cancervariants/variation-normalization

Unable to normalize HIST1H3B K28M

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bug
Dominant language
Python
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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

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