SAMD12

Chr 8AD

sterile alpha motif domain containing 12

Also known as: BAFME, BAFME1, FAME, FAME1, FCMTE1, MEBA

NCBI Gene: 401474 ENSG00000177570 UniProt: Q8N8I0 OMIM: 618073

SAMD12 encodes a protein predicted to function in cell surface receptor protein tyrosine kinase signaling at the cytoplasmic side of the plasma membrane. Mutations cause familial adult myoclonic epilepsy type 1, which follows autosomal dominant inheritance with adult onset as the name suggests. The gene shows tolerance to loss-of-function variants (pLI 0.001, LOEUF 1.14), indicating that complete loss of protein function may not be the primary disease mechanism.

OMIM ResearchSummary from RefSeq, OMIM

Predicted to be involved in cell surface receptor protein tyrosine kinase signaling pathway. Predicted to be active in cytoplasmic side of plasma membrane. Implicated in familial adult myoclonic epilepsy 1. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Epilepsy, familial adult myoclonic, 1MIM #601068

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Epilepsy, familial adult myoclonic; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.14

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.14LOEUF

pLI 0.001

Z-score 1.26

OE 0.58 (0.32–1.14)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.08Z-score

OE missense 1.02 (0.88–1.20)

109 obs / 106.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.58 (0.32–1.14)

0≤0.351.4

Missense OE?1.02 (0.88–1.20)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 6 / 10.4Missense obs/exp: 109 / 106.6Syn Z: -0.39

Background carrier burden — how many people carry a rare variant somewhere in SAMD12?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 320

255 rare PASS variants

Rare truncating (LoF)

1 in 5,900

41 rare PASS variants

Rare synonymous (reference)

1 in 530

94 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SAMD12. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 390	1 in 4,900
South Asian	~43k	1 in 200	1 in 5,400
Remaining (unassigned)	~30k	1 in 310	≈ 1 in 30,000
European (Finnish)	~27k	1 in 270	≈ 1 in 27,000
Admixed American	~22k	1 in 140	≈ 1 in 11,000
African / African American	~21k	1 in 140	≈ 1 in 6,000
East Asian	~20k	1 in 340	≈ 1 in 9,900
Ashkenazi Jewish	~13k	≈ 1 in 13,000	none seen
Middle Eastern	~2,884	1 in 170	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓