NSMAF

neutral sphingomyelinase activation associated factor, the group of WD repeat domain containing|GRAM domain containing|BEACH domain containing

Basic information

Region (hg38): 8:58583507-58659853

Links

ENSG00000035681 ∙ NCBI:8439 ∙ OMIM:603043 ∙ HGNC:8017 ∙ Uniprot:Q92636 ∙ 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 NSMAF gene.

• Inborn genetic diseases (28 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NSMAF 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			24			24
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			4		1	5
Total	0	0	28	0	1

Variants in NSMAF

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

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

Position	Type	Phenotype	Significance	ClinVar
8-58584123-A-G		not specified	Uncertain significance (Sep 26, 2023)
8-58586520-G-A		not specified	Uncertain significance (Aug 02, 2021)
8-58586547-G-C		not specified	Uncertain significance (Mar 29, 2023)
8-58586584-C-T		not specified	Uncertain significance (Nov 01, 2022)
8-58587656-G-T		not specified	Uncertain significance (Dec 11, 2023)
8-58587691-C-T		not specified	Uncertain significance (Jan 23, 2024)
8-58587692-C-T		not specified	Uncertain significance (Oct 28, 2023)
8-58589519-T-C		not specified	Uncertain significance (Aug 02, 2022)
8-58590041-C-T		not specified	Uncertain significance (Dec 03, 2021)
8-58595582-C-G		not specified	Uncertain significance (Sep 21, 2023)
8-58595603-T-C		not specified	Uncertain significance (Jan 23, 2024)
8-58597474-C-T		not specified	Uncertain significance (Aug 28, 2023)
8-58597500-A-C		not specified	Uncertain significance (Aug 30, 2022)
8-58599787-C-A		not specified	Uncertain significance (Jan 06, 2023)
8-58599800-C-T		not specified	Uncertain significance (Jan 31, 2024)
8-58599852-C-A		not specified	Uncertain significance (Dec 13, 2023)
8-58599854-T-C		not specified	Uncertain significance (Mar 16, 2022)
8-58601294-A-C		not specified	Uncertain significance (Sep 01, 2021)
8-58601477-G-A		not specified	Uncertain significance (Jan 19, 2022)
8-58601498-T-C		not specified	Uncertain significance (Dec 27, 2023)
8-58601546-G-GAAA		not specified	Benign (Mar 28, 2016)
8-58602120-T-C		not specified	Uncertain significance (Jul 06, 2021)
8-58602122-C-T		not specified	Uncertain significance (Dec 01, 2022)
8-58602136-A-T		not specified	Uncertain significance (Jun 27, 2022)
8-58605975-C-T		not specified	Uncertain significance (Feb 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NSMAF	protein_coding	protein_coding	ENST00000427130	31	76341

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.64e-12	1.00	125625	1	122	125748	0.000489

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.45	415	507	0.819	0.0000259	6237
Missense in Polyphen		159	201.61	0.78866		2478
Synonymous	1.55	162	189	0.857	0.0000109	1718
Loss of Function	3.52	28	56.6	0.495	0.00000248	721

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000984	0.000984
Ashkenazi Jewish	0.00	0.00
East Asian	0.000437	0.000435
Finnish	0.000878	0.000878
European (Non-Finnish)	0.000460	0.000457
Middle Eastern	0.000437	0.000435
South Asian	0.000604	0.000555
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Couples the p55 TNF-receptor (TNF-R55 / TNFR1) to neutral sphingomyelinase (N-SMASE). Specifically binds to the N- smase activation domain of TNF-R55. May regulate ceramide production by N-SMASE.
• Pathway: Sphingolipid signaling pathway - Homo sapiens (human);TNF alpha Signaling Pathway;Signal Transduction;ceramide signaling pathway;TNFR1-mediated ceramide production;TNF signaling;Death Receptor Signalling;TNFalpha;TNF receptor signaling pathway ;Ceramide signaling pathway (Consensus)

Recessive Scores

• pRec: 0.124

Intolerance Scores

• loftool: 0.381
• rvis_EVS: -0.13
• rvis_percentile_EVS: 44.03

Haploinsufficiency Scores

• pHI: 0.394
• hipred: Y
• hipred_score: 0.706
• ghis: 0.613

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.494

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nsmaf
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; hematopoietic system phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: nsmaf
• Affected structure: leukocyte
• Phenotype tag: abnormal
• Phenotype quality: cellular motility

Gene ontology

• Biological process: ceramide metabolic process;signal transduction;positive regulation of apoptotic process;positive regulation of catalytic activity;positive regulation of ceramide biosynthetic process
• Cellular component: cytoplasm;cytosol
• Molecular function: protein binding;sphingomyelin phosphodiesterase activator activity