# NC_012920.1(MT-TA):m.5600A>G

https://sugi.bio/variant/mt-ta-m-5600a-g

## Summary

**MT-TA m.5600A>G** is classified **Likely benign** in MT-TA (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-12). GnomAD v4.1's mitochondrial callset is not in our release; Associated with MELAS syndrome.

**At a glance:** Likely benign · review: Single submitter · rsID rs1603220045 · 1 submitter · 1 linked condition · gnomAD v4.1's mitochondrial callset is not in our release

## For patients & families {#patients}

This is a change in the MT-TA gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter, and is linked to MELAS 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.*

|  |  |
| --- | --- |
| Typical inheritance (of this condition) | Mitochondrial (maternal) |
| Age of onset (of this condition) | Adolescent, Adult, Childhood |
| Prevalence | 1-9 / 1 000 000 (Japan) |
| Clinical trials | 28 registered for this condition — see ClinicalTrials.gov |
| Diagnostic panels | MT-TA is a diagnostic-grade gene on 6 Genomics England panels |

**Commonly reported features of MELAS** (across patients with this condition; presentation varies — frequencies from Orphanet):

- Dementia — Very frequent (99-80%)
- Seizure — Very frequent (99-80%)
- Muscle weakness — Very frequent (99-80%)
- Migraine — Very frequent (99-80%)
- Increased circulating lactate concentration — Very frequent (99-80%)
- EEG abnormality — Very frequent (99-80%)
- Aphasia — Very frequent (99-80%)
- Stroke-like episode — Very frequent (99-80%)

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0007009/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [MT-TA](https://sugi.bio/atlas/gene/MT-TA/) |
| Coding change (HGVS c.) | m.5600A>G |
| dbSNP | [rs1603220045](https://www.ncbi.nlm.nih.gov/snp/rs1603220045/) |
| Variant type | single nucleotide variant |
| Location | chrMT:5600-5600 (GRCh38) |
| ClinVar | [VCV689951](https://www.ncbi.nlm.nih.gov/clinvar/variation/689951/) |

**All HGVS expressions:** `NC_012920.1:m.5600A>G`

## Computational & population evidence {#evidence}

- Non-coding constraint (Gnocchi): **not assessed** — the gnomAD non-coding genomic-constraint release is computed on the autosomes only, so chrMT has no window. That is a property of the dataset, not of the variant: it is not evidence that the region is unconstrained.
- SpliceAI: **not assessed** — no allele at this position is in our SpliceAI release, either because it lies outside the scored MANE transcript scope or because every allele is below Δ0.2. We cannot tell which, so this claims neither; absence is not evidence against a splicing effect.
- Population frequency: **gnomAD v4.1's mitochondrial callset is not in our release** — rarity (ACMG PM2) and BA1/BS1 cannot be assessed for this variant.

*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}


Curated gene–disease validity (ClinGen):

- **mitochondrial disease** — Definitive (MT)

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2019-07-12.

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

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine | Likely benign | criteria provided, single submitter | clinical testing | 2019-07-12 |

## Associated conditions {#conditions}

[MELAS syndrome](https://sugi.bio/atlas/disease/melas-syndrome/).

**Reported phenotype names (ClinVar):** MELAS syndrome, Juvenile myopathy, encephalopathy, lactic acidosis, stroke.

## Similar variants {#similar}

Related MT-TA variant pages (same residue, condition, or type): [MT-TA m.5591G>A](/variant/mt-ta-m-5591g-a), [MT-TA m.5590G>A](/variant/mt-ta-m-5590g-a), [MT-TA m.5607T>C](/variant/mt-ta-m-5607t-c), [MT-TA m.5609T>C](/variant/mt-ta-m-5609t-c), [MT-TA m.5619G>A](/variant/mt-ta-m-5619g-a), [MT-TA m.5645G>A](/variant/mt-ta-m-5645g-a), [MT-TA m.5654T>C](/variant/mt-ta-m-5654t-c), [MT-TA m.5592A>G](/variant/mt-ta-m-5592a-g).

### 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 689951). 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.*