SPECC1L

sperm antigen with calponin homology and coiled-coil domains 1 like

Basic information

Region (hg38): 22:24270817-24417739

Previous symbols: [ "CYTSA" ]

Links

ENSG00000100014 ∙ NCBI:23384 ∙ OMIM:614140 ∙ HGNC:29022 ∙ Uniprot:Q69YQ0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypertelorism, Teebi type (Supportive), mode of inheritance: AD
• commissural facial cleft (Supportive), mode of inheritance: AD
• Tessier number 4 facial cleft (Limited), mode of inheritance: AD
• autosomal dominant Opitz G/BBB syndrome (Moderate), mode of inheritance: AD
• hypertelorism, Teebi type (Moderate), mode of inheritance: AD
• hypertelorism, Teebi type (Definitive), mode of inheritance: AD
• autosomal dominant Opitz G/BBB syndrome (Strong), mode of inheritance: AD
• Tessier number 4 facial cleft (Strong), mode of inheritance: AD
• hypertelorism, Teebi type (Strong), mode of inheritance: AD
• autosomal dominant Opitz G/BBB syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Opitz GBBB syndrome, type II	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Neurologic	3398011; 17506099; 21703590; 25412741; 26111080

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPECC1L gene.

• Teebi hypertelorism syndrome 1 (2 variants)
• not provided (2 variants)
• Teebi hypertelorism syndrome (2 variants)
• SPECC1L-related syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPECC1L 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			1	36	6	43
missense	2	2	98	28	13	143
nonsense			6			6
start loss						0
frameshift			7			7
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)						0
splice region			5	6	1	12
non coding			3	9	13	25
Total	2	3	116	73	32

Variants in SPECC1L

This is a list of pathogenic ClinVar variants found in the SPECC1L region.

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

Position	Type	Phenotype	Significance	ClinVar
22-24302045-CA-C			Benign (May 19, 2021)
22-24302061-T-A			Benign (May 15, 2021)
22-24302187-T-C			Likely benign (Jul 01, 2022)
22-24302257-G-C			Uncertain significance (Apr 19, 2021)
22-24302272-T-C		Inborn genetic diseases	Uncertain significance (Aug 12, 2022)
22-24302276-T-C		SPECC1L-related disorder	Benign (Aug 01, 2024)
22-24302290-C-T		SPECC1L-related disorder	Likely benign (Oct 07, 2021)
22-24302291-G-T			Likely benign (Jan 21, 2022)
22-24302301-G-GA			Uncertain significance (Jan 21, 2024)
22-24302318-A-T		SPECC1L-related disorder	Uncertain significance (Apr 18, 2017)
22-24302337-A-G		Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
22-24302362-G-A			Uncertain significance (Jul 06, 2022)
22-24302383-A-G		SPECC1L-related disorder	Uncertain significance (Feb 16, 2023)
22-24302389-T-G		Teebi hypertelorism syndrome 1;Oculomaxillofacial dysostosis • SPECC1L-related disorder	Likely benign (Aug 01, 2024)
22-24311999-C-T			Likely benign (Jul 01, 2024)
22-24312061-C-T			Uncertain significance (Dec 01, 2023)
22-24312075-C-T			Uncertain significance (Apr 01, 2023)
22-24313295-A-G			Likely benign (Mar 04, 2023)
22-24313314-C-G			Uncertain significance (Nov 27, 2023)
22-24313323-G-T		Inborn genetic diseases	Uncertain significance (Nov 17, 2022)
22-24313359-C-T		Teebi hypertelorism syndrome 1	Likely pathogenic (Jun 01, 2022)
22-24313360-G-A			Likely benign (Nov 01, 2022)
22-24313373-G-A			Uncertain significance (-)
22-24313389-G-A		Inborn genetic diseases	Uncertain significance (Jun 14, 2023)
22-24313392-C-T		Inborn genetic diseases	Uncertain significance (Jun 03, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPECC1L	protein_coding	protein_coding	ENST00000314328	15	146923

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.859	0.141	125727	0	21	125748	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.60	497	608	0.818	0.0000365	7335
Missense in Polyphen		138	228.91	0.60286		2708
Synonymous	-0.106	230	228	1.01	0.0000134	2159
Loss of Function	5.49	11	54.9	0.200	0.00000363	624

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000185	0.000185
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000114	0.000114
Middle Eastern	0.00	0.00
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in cytokinesis and spindle organization. May play a role in actin cytoskeleton organization and microtubule stabilization and hence required for proper cell adhesion and migration. {ECO:0000269|PubMed:21703590}.
• Disease: DISEASE: Facial clefting, oblique, 1 (OBLFC1) [MIM:600251]: A rare form of facial clefting. A facial cleft is any of the fissures between the embryonic prominences that normally unite to form the face. {ECO:0000269|PubMed:21703590}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Opitz GBBB syndrome 2 (GBBB2) [MIM:145410]: A form of Opitz GBBB syndrome, a congenital midline malformation syndrome characterized by hypertelorism, genital-urinary defects such as hypospadias in males and splayed labia in females, cleft lip/palate, laryngotracheoesophageal abnormalities, imperforate anus, developmental delay and congenital heart defects. {ECO:0000269|PubMed:25412741}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.108

Intolerance Scores

• rvis_EVS: -0.28
• rvis_percentile_EVS: 33.53

Haploinsufficiency Scores

• pHI: 0.123
• hipred: N
• hipred_score: 0.332
• ghis: 0.406

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Specc1l
• Phenotype: embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cellular phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: specc1lb
• Affected structure: neural crest cell
• Phenotype tag: abnormal
• Phenotype quality: decreased occurrence

Gene ontology

• Biological process: cell cycle;cell adhesion;actin cytoskeleton organization;cell division
• Cellular component: microtubule organizing center;spindle;cytosol;gap junction;actin cytoskeleton;filamentous actin