# NM_007067.5(KAT7):c.532dup (p.Ser178fs)

https://sugi.bio/variant/kat7-p-ser178fs

## Summary

**KAT7 p.Ser178fs (c.532dup)** is classified **Uncertain significance** in KAT7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08).

**At a glance:** Uncertain significance · review: Single submitter · 1 submitter

## For patients & families {#patients}

This is a change in the KAT7 gene that is currently of uncertain significance — a definitive interpretation has not yet been established, submitted by 1 submitter.

*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:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [KAT7](https://sugi.bio/atlas/gene/KAT7/) |
| Protein change (HGVS p.) | p.Ser178fs |
| Coding change (HGVS c.) | c.532dup |
| MANE Select transcript | [NM_007067](https://www.ncbi.nlm.nih.gov/nuccore/NM_007067) |
| Variant type | Duplication |
| Location | chr17:49798507-49798508 (GRCh38) |
| ClinVar | [VCV4935774](https://www.ncbi.nlm.nih.gov/clinvar/variation/4935774/) |

**All HGVS expressions:** `NC_000017.10:g.47875872dup`, `NC_000017.11:g.49798510dup`, `NG_051976.1:g.14892dup`, `NG_051976.2:g.14831dup`, `NM_001199155.2:c.532dup`, `NM_001199156.2:c.163+6477dup`, `NM_001199157.2:c.340+1584dup`, `NM_001199158.2:c.163+6477dup`, `NM_001346706.2:c.340+1584dup`, `NM_007067.5:c.532dup`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP 9.956, GERP 1.71, phastCons 1 — highly conserved position (PP3-type support)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. the gene is **loss-of-function-intolerant** (LOEUF 0.275, pLI 1), supporting a loss-of-function disease mechanism. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in exon 4 of 15**, so the transcript is predicted to undergo NMD.
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no duplication variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

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

**KAT7** population constraint: LOEUF 0.275, pLI 1, missense-Z 4.3936. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}

Residue **178** lies in a modified residue (phosphoserine).

AlphaFold model confidence (whole protein): pLDDT 73.21, 41% of residues very-high.

**8 experimental structure(s)** (PDB): [5GK9](https://www.rcsb.org/structure/5GK9), [6MAJ](https://www.rcsb.org/structure/6MAJ), [6MAK](https://www.rcsb.org/structure/6MAK), [7D0O](https://www.rcsb.org/structure/7D0O), [7D0P](https://www.rcsb.org/structure/7D0P), [7D0Q](https://www.rcsb.org/structure/7D0Q).

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

*Describes the biological roles of KAT7 (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:** KAT7's established molecular role includes DNA replication origin binding.


### Pathways affected {#pathways}

KAT7 participates in **1 Reactome pathway** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [HATs acetylate histones](https://reactome.org/content/detail/R-HSA-3214847) | curated |

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

**Molecular function:** DNA replication origin binding, histone acetyltransferase activity, histone H4 acetyltransferase activity, histone H3K14 acetyltransferase activity, histone H3K23 acetyltransferase activity, histone H4K5 acetyltransferase activity.

**Biological process:** regulation of cell growth, regulation of DNA replication, regulation of DNA-templated transcription, internal peptidyl-lysine acetylation, regulation of DNA-templated DNA replication initiation, stress-activated protein kinase signaling cascade.

## Clinical significance {#significance}

**Uncertain significance** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2024-04-08.

**Submitter consensus:** unanimous (1/1 Uncertain significance).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Blueprint Genetics | Uncertain significance | criteria provided, single submitter | clinical testing | 2024-04-08 |

**Reported phenotype names (ClinVar):** not provided, none provided.

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-15); 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 4935774). 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.*