SAMD9

sterile alpha motif domain containing 9, the group of Sterile alpha motif domain containing

Basic information

Region (hg38): 7:93099513-93118023

Previous symbols: [ "C7orf5" ]

Links

ENSG00000205413 ∙ NCBI:54809 ∙ OMIM:610456 ∙ HGNC:1348 ∙ Uniprot:Q5K651 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• MIRAGE syndrome (Definitive), mode of inheritance: AD
• MIRAGE syndrome (Moderate), mode of inheritance: AD
• normophosphatemic familial tumoral calcinosis (Moderate), mode of inheritance: AR
• normophosphatemic familial tumoral calcinosis (Supportive), mode of inheritance: AR
• MIRAGE syndrome (Supportive), mode of inheritance: AD
• MIRAGE syndrome (Definitive), mode of inheritance: AD
• normophosphatemic familial tumoral calcinosis (Moderate), mode of inheritance: AR
• monosomy 7 myelodysplasia and leukemia syndrome 2 (Limited), mode of inheritance: AD
• monosomy 7 myelodysplasia and leukemia syndrome 2 (Limited), mode of inheritance: Unknown
• MIRAGE syndrome (Strong), mode of inheritance: AD
• normophosphatemic familial tumoral calcinosis (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mirage syndrome; Monosomy 7 myelodysplasia and leukemia syndrome 2; Tumoral calcinosis, normophosphatemic, familial	AD/AR	Allergy/Immunology/Infectious; Endocrine; Hematologic; Musculoskeletal; Oncologic	Mirage syndrome can include anemia and thrombocytopenia requiring transfusions; Individuals can have severe and recurrent infections, and awareness may allow preventive measures and early and aggressive treatment of infections; Individuals may have salt-wasting adrenal hypoplasia, and awareness may allow prompt recognition and treatment to manage electrolyte and endocrine sequelae; For individuals with Tumoral calcinosis, surveillance/early treatment of tumoral calcinosis may reduce morbidity; Monosomy 7 myelodysplasia and leukemia syndrome 2 involves germline genetic anomaly as well as associated somatic loss of chromosome 7, and results in increased risk of hematologic malignancy such that awareness may allow early diagnosis and management of disease	Allergy/Immunology/Infectious; Dental; Dermatologic; Endocrine; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic	3366131; 15133511; 16960814; 18094730; 27182967; 28487541; 30046003; 30322869

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SAMD9 gene.

• Inborn_genetic_diseases (1469 variants)
• not_provided (1261 variants)
• not_specified (130 variants)
• SAMD9-related_disorder (109 variants)
• MIRAGE_syndrome (70 variants)
• Monosomy_7_myelodysplasia_and_leukemia_syndrome_2 (48 variants)
• Normophosphatemic_familial_tumoral_calcinosis (43 variants)
• Hereditary_cancer-predisposing_syndrome (3 variants)
• See_cases (3 variants)
• Intellectual_disability (2 variants)
• Familial_thoracic_aortic_aneurysm_and_aortic_dissection (1 variants)
• Myelodysplastic_syndrome (1 variants)
• Hereditary_cancer (1 variants)
• Diffuse_midline_glioma,_H3_K27-altered (1 variants)
• Ataxia-pancytopenia_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SAMD9 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000017654.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	631	1	635
missense	8	27	1278	84	7	1404
nonsense		5	53	1		59
start loss			2			2
frameshift	1	4	67	4		76
splice donor/acceptor (+/-2bp)			1			1
Total	9	36	1404	720	8

Highest pathogenic variant AF is 0.0000254068

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SAMD9	protein_coding	protein_coding	ENST00000379958	1	18508

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.05e-33	0.0000242	124725	6	1008	125739	0.00404

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.769	709	769	0.922	0.0000384	10594
Missense in Polyphen		173	186.49	0.92767		2651
Synonymous	0.0796	277	279	0.994	0.0000141	2894
Loss of Function	0.104	51	51.8	0.984	0.00000288	751

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0363	0.0362
Ashkenazi Jewish	0.00	0.00
East Asian	0.00256	0.00256
Finnish	0.000464	0.000462
European (Non-Finnish)	0.00178	0.00178
Middle Eastern	0.00256	0.00256
South Asian	0.00304	0.00304
Other	0.00278	0.00277

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in the inflammatory response to tissue injury and the control of extra-osseous calcification, acting as a downstream target of TNF-alpha signaling. Involved in the regulation of EGR1, in coordination with RGL2. May be involved in endosome fusion. {ECO:0000269|PubMed:16960814, ECO:0000269|PubMed:18094730, ECO:0000269|PubMed:21160498, ECO:0000269|PubMed:24029230}.
• Disease: DISEASE: Tumoral calcinosis, normophosphatemic, familial (NFTC) [MIM:610455]: An uncommon, life-threatening disorder characterized by progressive deposition of calcified masses in cutaneous and subcutaneous tissues. Serum phosphate levels are normal. Clinical features include painful calcified ulcerative lesions and massive calcium deposition in the mid- and lower dermis, severe skin and bone infections, erythematous papular skin eruption in infancy, conjunctivitis, and gingivitis. NFTC shows a striking resemblance to acquired dystrophic calcinosis, in which tissue calcification occurs as a consequence of tissue injury/inflammation. {ECO:0000269|PubMed:16960814, ECO:0000269|PubMed:18094730}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: MIRAGE syndrome (MIRAGE) [MIM:617053]: A form of syndromic adrenal hypoplasia characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. {ECO:0000269|PubMed:27182967}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0928

Intolerance Scores

• loftool: 0.991
• rvis_EVS: 1.12
• rvis_percentile_EVS: 92.11

Haploinsufficiency Scores

• pHI: 0.115
• hipred: N
• hipred_score: 0.112
• ghis: 0.437

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.258

Gene Damage Prediction

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

Gene ontology

• Biological process: endosomal vesicle fusion
• Cellular component: cytoplasm;cytosol;intracellular membrane-bounded organelle
• Molecular function: protein binding