SPAG1

sperm associated antigen 1, the group of R2SP complex|Axonemal dynein assembly factors|Tetratricopeptide repeat domain containing

Basic information

Region (hg38): 8:100157906-100259278

Links

ENSG00000104450 ∙ NCBI:6674 ∙ OMIM:603395 ∙ HGNC:11212 ∙ Uniprot:Q07617 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary ciliary dyskinesia 28 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia 28 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia (Supportive), mode of inheritance: AD
• primary ciliary dyskinesia 28 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ciliary dyskinesia, primary, 28	AR	Allergy/Immunology/Infectious; Pulmonary	Individuals are described as at risk of neonatal respiratory distress and recurrent sinopulmonary infections, and respiratory interventions, as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial	Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Pulmonary	24055112

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPAG1 gene.

• Primary ciliary dyskinesia 28 (33 variants)
• Primary ciliary dyskinesia (3 variants)
• Autosomal dominant nocturnal frontal lobe epilepsy 5 (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPAG1 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			3	80	4	87
missense			153	11	5	169
nonsense	9	2	1			12
start loss						0
frameshift	23	3	2			28
inframe indel	1		3		1	5
splice donor/acceptor (+/-2bp)	1	6	1		1	9
splice region			4	13		17
non coding	1		2	51	42	96
Total	35	11	165	142	53

Highest pathogenic variant AF is 0.0000593

Variants in SPAG1

This is a list of pathogenic ClinVar variants found in the SPAG1 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-100161958-A-C			Benign (Aug 13, 2019)
8-100162160-C-T			Likely benign (Nov 12, 2018)
8-100162198-G-A			Benign (Apr 20, 2019)
8-100162282-T-G		Primary ciliary dyskinesia 28	Pathogenic (Oct 03, 2013)
8-100162296-T-C		Primary ciliary dyskinesia 28	Uncertain significance (Oct 17, 2022)
8-100162368-A-G		Primary ciliary dyskinesia • Primary ciliary dyskinesia 28	Uncertain significance (Jul 28, 2022)
8-100162369-T-C		Primary ciliary dyskinesia 28	Uncertain significance (Feb 19, 2019)
8-100162383-G-A		Primary ciliary dyskinesia	Uncertain significance (Aug 08, 2023)
8-100162385-T-G		Primary ciliary dyskinesia 28	Uncertain significance (Aug 09, 2022)
8-100162406-T-G		Primary ciliary dyskinesia 28	Uncertain significance (Dec 06, 2023)
8-100162412-C-T		Primary ciliary dyskinesia 28 • Primary ciliary dyskinesia	Likely benign (Nov 10, 2023)
8-100162413-G-A		Primary ciliary dyskinesia 28 • Primary ciliary dyskinesia	Uncertain significance (Mar 15, 2024)
8-100162421-G-A		Primary ciliary dyskinesia 28	Likely pathogenic (Aug 31, 2018)
8-100162715-C-T			Benign (Nov 27, 2018)
8-100165529-C-A			Benign (Dec 31, 2018)
8-100165538-C-T			Benign (Dec 31, 2018)
8-100165607-C-T			Likely benign (Jan 16, 2019)
8-100165766-G-T			Likely benign (Apr 06, 2020)
8-100165798-T-C		Primary ciliary dyskinesia 28	Likely benign (Nov 11, 2023)
8-100165814-A-T		Primary ciliary dyskinesia 28 • Primary ciliary dyskinesia	Uncertain significance (May 13, 2024)
8-100165819-G-A		Primary ciliary dyskinesia 28	Uncertain significance (Oct 24, 2018)
8-100165878-G-A		Primary ciliary dyskinesia 28 • Primary ciliary dyskinesia • SPAG1-related disorder	Conflicting classifications of pathogenicity (Nov 27, 2023)
8-100165881-C-G		Primary ciliary dyskinesia • Primary ciliary dyskinesia 28	Uncertain significance (Apr 22, 2022)
8-100165907-T-TA		Primary ciliary dyskinesia 28	Pathogenic (Oct 28, 2022)
8-100165912-C-T		Primary ciliary dyskinesia 28	Uncertain significance (Aug 09, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPAG1	protein_coding	protein_coding	ENST00000388798	18	101373

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.45e-9	0.997	125645	0	103	125748	0.000410

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.908	376	429	0.877	0.0000215	6041
Missense in Polyphen		127	162.27	0.78265		2142
Synonymous	2.20	119	154	0.774	0.00000813	1690
Loss of Function	2.75	21	39.7	0.529	0.00000184	607

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000276	0.000276
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000949	0.0000924
European (Non-Finnish)	0.000469	0.000466
Middle Eastern	0.000163	0.000163
South Asian	0.00133	0.00127
Other	0.000172	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in the cytoplasmic assembly of the ciliary dynein arms (By similarity). May play a role in fertilization. Binds GTP and has GTPase activity. {ECO:0000250, ECO:0000269|PubMed:11517287, ECO:0000269|PubMed:1299558}.

Recessive Scores

• pRec: 0.168

Intolerance Scores

• loftool: 0.955
• rvis_EVS: 0.8
• rvis_percentile_EVS: 87.69

Haploinsufficiency Scores

• pHI: 0.0594
• hipred: N
• hipred_score: 0.217
• ghis: 0.474

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.628

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Spag1

Zebrafish Information Network

• Gene name: spag1a
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: curved dorsal

Gene ontology

• Biological process: single fertilization;axonemal dynein complex assembly
• Cellular component: cytoplasm;cytosol
• Molecular function: GTP binding;hydrolase activity