SAMD12

protein-coding

sterile alpha motif domain containing 12, the group of Sterile alpha motif domain containing

Gene summary

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]

MANE transcript

NM_207506.3

Inheritance

SD, AD

ClinVar variants

U:35B:4

Top phenotype

Epilepsy, familial adult myoclonic, 1

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr8:118,189,455-118,622,112

External References & Databases

Ensembl (ENSG00000177570)

Transcript & Mutation Effects

hg38 • Region Span ~432.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

epilepsy, familial adult myoclonic, 1LIMITED

Inheritance Pattern: SD

Disease ID:MONDO:0010985

Submitter: PanelApp Australia

benign adult familial myoclonic epilepsySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019448

Submitter: Orphanet

epilepsy, familial adult myoclonic, 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0010985

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Epilepsy, familial adult myoclonic, 1AD

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 29939203

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SAMD12 variants in ClinVar

5 Conditions Cataloged

Inborn genetic diseasesTotal: 27

not providedTotal: 4

Epilepsy, familial adult myoclonic, 1Total: 2

not specifiedTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_207506.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			30 clinvar	3 clinvar		33
nonsense						0
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	35	4	0	39

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_207506.3	RefSeq	NP_997389.2	4	MANE Select
ENST00000314727.9	Ensembl	ENSP00000314173.4	4	MANE Select
NM_001101676.2	RefSeq	NP_001095146.1	5	Standard
NM_001349811.2	RefSeq	NP_001336740.1	5	Standard

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000314727
Coding exons: 4
Length: 432537
Individuals with no LoFs: 125690
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125697
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0826	109	107	1.02	0.00000548	1293
Missense (PolyPhen)		43	41.319	1.0407		483
Synonymous	-0.394	45	41.8	1.08	0.00000211	386
Loss of Function	1.26	6	10.4	0.579	6.94e-7	95

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0731

Intolerance Scores

LoFtool: 0.360
RVIS EVS: 0.33
RVIS percentile EVS: 73.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.175

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium