# NM_015909.3:c.(?_5028)_(5724_?)del

https://sugi.bio/variant/nbas-c-5028

## Summary

**NBAS c.(?_5028** is classified **Likely pathogenic** in NBAS (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-06). Associated with short stature-optic atrophy-Pelger-Huët anomaly syndrome.

**At a glance:** Likely pathogenic · review: Single submitter · 1 submitter · 1 linked condition

## For patients & families {#patients}

This is a change in the NBAS gene that is considered likely disease-causing, submitted by 1 submitter, and is linked to short stature-optic atrophy-Pelger-Huët anomaly syndrome.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0010945/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [NBAS](https://sugi.bio/atlas/gene/NBAS/) |
| Coding change (HGVS c.) | c.(?_5028 |
| MANE Select transcript | [NM_015909](https://www.ncbi.nlm.nih.gov/nuccore/NM_015909) |
| Variant type | Deletion |
| ClinVar | [VCV624565](https://www.ncbi.nlm.nih.gov/clinvar/variation/624565/) |

## Gene constraint & dosage {#gene-context}

**NBAS** population constraint: LOEUF 0.761, pLI 2.4931e-43, missense-Z 0.22195; ClinGen dosage — haploinsufficiency gene assoc. with recessive phenotype, triplosensitivity Not yet evaluated/3. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 74.42, 4% of residues very-high.

## What this gene does {#gene-function}

*Describes the biological roles of NBAS (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** NBAS's established molecular role includes SNARE binding.


### Pathways affected {#pathways}

NBAS participates in **1 Reactome pathway** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [COPI-dependent Golgi-to-ER retrograde traffic](https://reactome.org/content/detail/R-HSA-6811434) | curated |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** SNARE binding.

**Biological process:** nuclear-transcribed mRNA catabolic process, retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum, negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay.

## Clinical significance {#significance}

**Likely pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2018-08-06.

**Submitter consensus:** unanimous (1/1 Likely pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota | Likely pathogenic | criteria provided, single submitter | clinical testing | 2018-08-06 |

## Associated conditions {#conditions}

[short stature-optic atrophy-Pelger-Huët anomaly syndrome](https://sugi.bio/atlas/disease/short-stature-optic-atrophy-pelger-hu-t-anomaly-syndrome/).

**Reported phenotype names (ClinVar):** Short stature-optic atrophy-Pelger-Huët anomaly syndrome, Short stature, optic nerve atrophy, and Pelger-Huet anomaly, Short stature-optic atrophy-Pelger-HuC+t anomaly syndrome.

## Similar variants {#similar}

Related NBAS variant pages (same residue, condition, or type): [NBAS p.Asp2149_Ile2150insTer](/variant/nbas-p-asp2149-ile2150inster), [NBAS p.Ile984fs](/variant/nbas-p-ile984fs), [NBAS p.Leu1726fs](/variant/nbas-p-leu1726fs), [NBAS p.Ser1419fs](/variant/nbas-p-ser1419fs), [NBAS c.4657_4659+18del](/variant/nbas-c-4657-4659-plus-18del), [NBAS p.Ala1686fs](/variant/nbas-p-ala1686fs), [NBAS p.Phe1701_Met1702insTer](/variant/nbas-p-phe1701-met1702inster), [NBAS p.Ile512fs](/variant/nbas-p-ile512fs).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-14); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 624565). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*