ADAMTS10

ADAM metallopeptidase with thrombospondin type 1 motif 10, the group of ADAM metallopeptidases with thrombospondin type 1 motif

Basic information

Region (hg38): 19:8580240-8610735

Links

ENSG00000142303 ∙ NCBI:81794 ∙ OMIM:608990 ∙ HGNC:13201 ∙ Uniprot:Q9H324 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Weill-Marchesani syndrome 1 (Moderate), mode of inheritance: AR
• Weill-Marchesani syndrome (Supportive), mode of inheritance: AD
• Weill-Marchesani syndrome 1 (Definitive), mode of inheritance: AR
• Weill-Marchesani syndrome 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Weill-Marchesani syndrome 1	AR	Cardiovascular; Ophthalmologic	Individuals can have cardiac anomalies, including long QTc, and awareness may allow for preventive/medical management, which may decrease morbidity and mortality; As the condition can include glaucoma, surveillance can allow early interventions that may potentially be beneficial related to preservation of visual status	Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic	11941487; 14598350; 15368195; 17663475

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADAMTS10 gene.

• not provided (13 variants)
• Weill-Marchesani syndrome 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADAMTS10 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			5	218	6	229
missense		6	290	9	6	311
nonsense	8	1				9
start loss						0
frameshift	5	1	1			7
inframe indel			2			2
splice donor/acceptor (+/-2bp)		2				2
splice region			15	49	3	67
non coding			29	135	43	207
Total	13	10	327	362	55

Variants in ADAMTS10

This is a list of pathogenic ClinVar variants found in the ADAMTS10 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-8580263-G-A		Weill-Marchesani syndrome	Uncertain significance (Jan 12, 2018)
19-8580315-G-T		Weill-Marchesani syndrome	Uncertain significance (Jan 13, 2018)
19-8580330-G-T		Weill-Marchesani syndrome	Uncertain significance (Jan 13, 2018)
19-8580436-AC-A		Weill-Marchesani syndrome	Uncertain significance (Jun 14, 2016)
19-8580436-A-AC		Weill-Marchesani syndrome	Uncertain significance (Jun 14, 2016)
19-8580444-C-G		Weill-Marchesani syndrome	Benign (Jan 12, 2018)
19-8580446-C-A		Weill-Marchesani syndrome	Uncertain significance (Jan 13, 2018)
19-8580465-T-C		Weill-Marchesani syndrome	Benign (Jan 13, 2018)
19-8580482-G-A		Weill-Marchesani syndrome	Uncertain significance (Jan 12, 2018)
19-8580537-C-T		Weill-Marchesani syndrome	Uncertain significance (Jan 13, 2018)
19-8580563-T-A		Weill-Marchesani syndrome	Uncertain significance (Jan 13, 2018)
19-8580571-G-A		Weill-Marchesani syndrome	Uncertain significance (Jan 12, 2018)
19-8580582-T-C		Weill-Marchesani syndrome	Uncertain significance (Jan 13, 2018)
19-8580634-C-T		Weill-Marchesani syndrome	Benign/Likely benign (Apr 12, 2019)
19-8580654-A-AG		Weill-Marchesani syndrome	Benign/Likely benign (Jul 31, 2018)
19-8580684-G-A		Weill-Marchesani syndrome	Uncertain significance (Jan 13, 2018)
19-8580722-C-T		Weill-Marchesani syndrome	Likely benign (Aug 20, 2018)
19-8580736-C-T		Weill-Marchesani syndrome	Uncertain significance (Jan 12, 2018)
19-8580747-C-T		Weill-Marchesani syndrome	Uncertain significance (Jan 12, 2018)
19-8580807-G-GC		Weill-Marchesani syndrome	Uncertain significance (Nov 01, 2022)
19-8580812-C-A		Weill-Marchesani syndrome	Uncertain significance (Jan 12, 2018)
19-8580812-C-G		Weill-Marchesani syndrome	Uncertain significance (Jan 12, 2018)
19-8580846-T-C		Weill-Marchesani syndrome	Uncertain significance (Jan 13, 2018)
19-8580857-A-G		Weill-Marchesani syndrome	Uncertain significance (Jan 12, 2018)
19-8580873-C-T		Weill-Marchesani syndrome	Benign/Likely benign (May 11, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADAMTS10	protein_coding	protein_coding	ENST00000270328	24	30495

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.843	0.157	125730	0	18	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.63	446	720	0.620	0.0000507	7077
Missense in Polyphen		109	255.08	0.42732		2605
Synonymous	0.782	294	312	0.944	0.0000238	2241
Loss of Function	5.67	12	59.0	0.204	0.00000313	618

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000342	0.000333
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000163	0.000163
Finnish	0.0000479	0.0000462
European (Non-Finnish)	0.0000532	0.0000527
Middle Eastern	0.000163	0.000163
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Metalloprotease that participate in microfibrils assembly. Microfibrils are extracellular matrix components occurring independently or along with elastin in the formation of elastic tissues. {ECO:0000269|PubMed:21402694}.
• Disease: DISEASE: Weill-Marchesani syndrome 1 (WMS1) [MIM:277600]: A rare connective tissue disorder characterized by short stature, brachydactyly, joint stiffness, and eye abnormalities including microspherophakia, ectopia lentis, severe myopia and glaucoma. {ECO:0000269|PubMed:15368195, ECO:0000269|PubMed:18567016}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Post-translational protein modification;Metabolism of proteins;O-glycosylation of TSR domain-containing proteins;O-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.121

Intolerance Scores

• loftool: 0.476
• rvis_EVS: -1.32
• rvis_percentile_EVS: 4.78

Haploinsufficiency Scores

• pHI: 0.288
• hipred: Y
• hipred_score: 0.693
• ghis: 0.618

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.221

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adamts10

Gene ontology

• Biological process: proteolysis;biological_process
• Cellular component: microfibril;collagen-containing extracellular matrix
• Molecular function: molecular_function;metalloendopeptidase activity;protein binding;metal ion binding