TSPEAR

thrombospondin type laminin G domain and EAR repeats

Basic information

Region (hg38): 21:44497893-44711572

Previous symbols: [ "C21orf29", "DFNB98" ]

Links

ENSG00000175894 ∙ NCBI:54084 ∙ OMIM:612920 ∙ HGNC:1268 ∙ Uniprot:Q8WU66 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 98 (Disputed Evidence), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 98 (Limited), mode of inheritance: AR
• ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis (Moderate), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 98 (Limited), mode of inheritance: AR
• ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis (Strong), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Disputed Evidence), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 98	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Dental; Dermatologic	22678063; 27736875; 30046887; 32112661; 34042254

ClinVar

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

• not provided (27 variants)
• Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis (3 variants)
• Tooth agenesis, selective, 10 (2 variants)
• Autosomal recessive nonsyndromic hearing loss 98 (1 variants)
• Ectodermal dysplasia 14, hair/tooth type, with hypohidrosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TSPEAR 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	74	7	82
missense		4	149	12	1	166
nonsense	13	1	2			16
start loss			1			1
frameshift	12	7	1			20
inframe indel			1			1
splice donor/acceptor (+/-2bp)	3	4	2			9
splice region			9	7		16
non coding			295	141	44	480
Total	28	16	452	227	52

Highest pathogenic variant AF is 0.0000798

Variants in TSPEAR

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

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

Position	Type	Phenotype	Significance	ClinVar
21-44499733-G-T			Likely benign (Nov 25, 2020)
21-44499743-CCCACCTGGCCACCCCAGTTGCTGCCGGGCAGCCGCGGCCTCAGCGTGTCCTCAG-C			Uncertain significance (May 02, 2024)
21-44499769-G-A			Likely benign (May 28, 2021)
21-44499778-C-T			Likely benign (Mar 19, 2020)
21-44499779-G-A			Likely benign (Nov 30, 2018)
21-44499787-C-T		Inborn genetic diseases	Uncertain significance (Dec 21, 2023)
21-44499798-C-T			Likely benign (Mar 08, 2023)
21-44499799-C-T			Uncertain significance (Sep 15, 2022)
21-44499800-G-A			Uncertain significance (Sep 06, 2023)
21-44499814-A-C		Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 27, 2023)
21-44499821-C-T			Uncertain significance (Jul 17, 2022)
21-44499827-C-T			Likely benign (Jan 09, 2023)
21-44499828-G-A			Likely benign (Oct 24, 2022)
21-44499855-C-T		TSPEAR-related disorder	Likely benign (Jun 07, 2022)
21-44499856-G-A		not specified • Inborn genetic diseases	Uncertain significance (Sep 27, 2022)
21-44499856-G-T			Uncertain significance (May 01, 2023)
21-44499859-G-A			Uncertain significance (Aug 19, 2022)
21-44499868-G-A		Inborn genetic diseases	Uncertain significance (Dec 19, 2023)
21-44499868-G-C		not specified	Uncertain significance (May 28, 2015)
21-44499873-C-T			Uncertain significance (Mar 31, 2021)
21-44499875-A-G		Inborn genetic diseases	Uncertain significance (Jan 02, 2024)
21-44499878-C-T		not specified • Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis • Inborn genetic diseases • Autosomal recessive nonsyndromic hearing loss 98 • Tooth agenesis, selective, 10 • TSPEAR-related disorder	Conflicting classifications of pathogenicity (Sep 20, 2024)
21-44499883-C-T			Conflicting classifications of pathogenicity (Oct 23, 2023)
21-44499887-C-T		Inborn genetic diseases	Uncertain significance (Jan 09, 2024)
21-44499888-G-A			Likely benign (Jul 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TSPEAR	protein_coding	protein_coding	ENST00000323084	12	213721

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.44e-17	0.0298	125390	1	357	125748	0.00142

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.952	473	418	1.13	0.0000274	4307
Missense in Polyphen		128	103.24	1.2399		1186
Synonymous	-0.540	201	191	1.05	0.0000143	1396
Loss of Function	0.675	28	32.1	0.872	0.00000177	318

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00158	0.00155
Ashkenazi Jewish	0.000202	0.000198
East Asian	0.000875	0.000870
Finnish	0.000373	0.000370
European (Non-Finnish)	0.00232	0.00224
Middle Eastern	0.000875	0.000870
South Asian	0.00109	0.00105
Other	0.000985	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in development or function of the auditory system.
• Disease: DISEASE: Deafness, autosomal recessive, 98 (DFNB98) [MIM:614861]: A form of non-syndromic sensorineural hearing loss with prelingual onset. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:22678063}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.128

Intolerance Scores

• rvis_EVS: -1.08
• rvis_percentile_EVS: 7.32

Haploinsufficiency Scores

• pHI: 0.131
• hipred: N
• hipred_score: 0.264
• ghis: 0.510

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• 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: Tspear

Gene ontology

• Biological process: sensory perception of sound
• Cellular component: extracellular region;cell surface;stereocilium;ciliary membrane
• Molecular function: molecular_function