SAMD8

sterile alpha motif domain containing 8, the group of Sterile alpha motif domain containing

Basic information

Region (hg38): 10:75099586-75182123

Links

ENSG00000156671 ∙ NCBI:142891 ∙ OMIM:611575 ∙ HGNC:26320 ∙ Uniprot:Q96LT4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SAMD8 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SAMD8 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			11			11
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	11	0	0

Variants in SAMD8

This is a list of pathogenic ClinVar variants found in the SAMD8 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-75103934-G-A			Benign (Jun 21, 2018)
10-75103972-G-A			Benign (Jun 05, 2018)
10-75109140-G-C			Likely benign (Dec 01, 2022)
10-75150556-C-T		not specified	Uncertain significance (Feb 27, 2024)
10-75150594-G-C		not specified	Uncertain significance (Nov 12, 2021)
10-75150707-A-G		not specified	Uncertain significance (Jan 26, 2023)
10-75150783-G-T		not specified	Uncertain significance (Feb 27, 2024)
10-75150877-C-T		not specified	Uncertain significance (Jan 07, 2025)
10-75150887-A-G		not specified	Uncertain significance (Oct 20, 2023)
10-75150968-C-G		not specified	Uncertain significance (Jan 21, 2025)
10-75168545-A-G		not specified	Uncertain significance (Jun 04, 2024)
10-75176120-T-C		not specified	Uncertain significance (Mar 04, 2024)
10-75176559-A-G		not specified	Uncertain significance (Mar 06, 2023)
10-75176616-A-G		not specified	Uncertain significance (Mar 28, 2024)
10-75176624-G-A		not specified	Uncertain significance (May 28, 2023)
10-75176648-T-C		not specified	Uncertain significance (Sep 26, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SAMD8	protein_coding	protein_coding	ENST00000542569	5	82538

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00176	0.993	125725	0	21	125746	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.89	101	222	0.455	0.0000109	2751
Missense in Polyphen		24	82.059	0.29247		1050
Synonymous	0.459	72	77.1	0.934	0.00000383	784
Loss of Function	2.47	8	19.9	0.402	0.00000131	205

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.000370	0.000370
European (Non-Finnish)	0.0000704	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Sphingomyelin synthases synthesize sphingolipids through transfer of a phosphatidyl head group on to the primary hydroxyl of ceramide. SAMD8 is an endoplasmic reticulum (ER) transferase that has no sphingomyelin synthase activity but can convert phosphatidylethanolamine (PE) and ceramide to ceramide phosphoethanolamine (CPE) albeit with low product yield. Appears to operate as a ceramide sensor to control ceramide homeostasis in the endoplasmic reticulum rather than a converter of ceramides. Seems to be critical for the integrity of the early secretory pathway. {ECO:0000269|PubMed:19506037}.
• Pathway: Metabolism of lipids;sphingomyelin metabolism/ceramide salvage;Metabolism;Sphingolipid de novo biosynthesis;Sphingolipid metabolism (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.357
• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.64

Haploinsufficiency Scores

• pHI: 0.304
• hipred: Y
• hipred_score: 0.543
• ghis: 0.536

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.141

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Samd8
• Phenotype: homeostasis/metabolism phenotype

Gene ontology

• Biological process: sphingomyelin biosynthetic process;sphingolipid biosynthetic process;ceramide biosynthetic process;ceramide phosphoethanolamine biosynthetic process;regulation of ceramide biosynthetic process
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;cytosol;integral component of plasma membrane;integral component of membrane;integral component of Golgi membrane;integral component of endoplasmic reticulum membrane
• Molecular function: ceramide phosphoethanolamine synthase activity;molecular_function;sphingomyelin synthase activity;ceramide cholinephosphotransferase activity