SMOC1

SPARC related modular calcium binding 1, the group of SPARC family

Basic information

Region (hg38): 14:69854130-70032366

Links

ENSG00000198732 ∙ NCBI:64093 ∙ OMIM:608488 ∙ HGNC:20318 ∙ Uniprot:Q9H4F8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microphthalmia with limb anomalies (Definitive), mode of inheritance: AR
• microphthalmia with limb anomalies (Strong), mode of inheritance: AR
• microphthalmia with limb anomalies (Supportive), mode of inheritance: AR
• microphthalmia with limb anomalies (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microphthalmia with limb anomalies	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal; Ophthalmologic	21194678; 21194680

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMOC1 gene.

• not provided (81 variants)
• Inborn genetic diseases (17 variants)
• Microphthalmia with limb anomalies (9 variants)
• not specified (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMOC1 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	21	4	26
missense			25	4	2	31
nonsense	3					3
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			1	3	1	5
non coding				5	25	30
Total	4	1	26	30	31

Highest pathogenic variant AF is 0.0000394

Variants in SMOC1

This is a list of pathogenic ClinVar variants found in the SMOC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-69879262-T-A			Benign (May 19, 2021)
14-69879273-T-A			Benign (May 15, 2021)
14-69879633-G-A			Benign (May 15, 2021)
14-69879696-C-G		Inborn genetic diseases	Uncertain significance (Apr 25, 2023)
14-69879699-C-T			Benign/Likely benign (Dec 13, 2023)
14-69879710-C-T		Inborn genetic diseases	Uncertain significance (Jan 31, 2024)
14-69879726-G-A			Uncertain significance (Oct 01, 2014)
14-69879729-G-A			Likely benign (Aug 09, 2023)
14-69879739-C-T			Likely benign (Sep 18, 2022)
14-69879745-C-T			Uncertain significance (Jan 13, 2024)
14-69952081-G-A			Benign (May 19, 2021)
14-69952141-C-G		SMOC1-related disorder	Benign/Likely benign (Jan 18, 2024)
14-69952153-C-T			Uncertain significance (Jul 23, 2023)
14-69952164-G-A		not specified • Microphthalmia with limb anomalies	Benign (Jan 31, 2024)
14-69952170-C-A		Inborn genetic diseases	Uncertain significance (Jan 17, 2024)
14-69952173-C-T			Likely benign (Dec 31, 2019)
14-69952201-A-T		SMOC1-related disorder	Likely benign (Dec 23, 2023)
14-69952227-C-T		SMOC1-related disorder	Likely benign (Aug 19, 2022)
14-69952228-G-A		Inborn genetic diseases	Uncertain significance (Sep 14, 2023)
14-69952261-C-T		Microphthalmia with limb anomalies	Likely pathogenic (Nov 23, 2017)
14-69952262-G-A			Uncertain significance (May 01, 2019)
14-69952268-C-T		SMOC1-related disorder	Conflicting classifications of pathogenicity (Jan 26, 2024)
14-69952271-C-T			Uncertain significance (Aug 04, 2023)
14-69952273-C-G			Uncertain significance (Aug 22, 2022)
14-69952282-G-A			Benign (Jan 19, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMOC1	protein_coding	protein_coding	ENST00000361956	12	178236

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00947	0.990	125715	0	29	125744	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.743	214	247	0.867	0.0000151	2822
Missense in Polyphen		74	111.81	0.66185		1284
Synonymous	1.55	79	98.6	0.801	0.00000616	845
Loss of Function	3.08	8	24.4	0.328	0.00000130	281

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000553	0.000553
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000618	0.0000615
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays essential roles in both eye and limb development. Probable regulator of osteoblast differentiation. {ECO:0000269|PubMed:20359165, ECO:0000269|PubMed:21194678, ECO:0000269|PubMed:21194680}.
• Disease: DISEASE: Ophthalmoacromelic syndrome (OAS) [MIM:206920]: A rare disorder presenting with ocular anomalies, ranging from mild microphthalmia to true anophthalmia, and limb anomalies. Limb malformations include fused 4th and 5th metacarpals and short 5th finger in hands, and oligodactyly in foot (four toes). Most patients have bilateral anophthalmia/ microphthalmia, but unilateral abnormality is also noted. Other malformations are rare, but venous or vertebral anomaly was recognized each in single cases. {ECO:0000269|PubMed:21194678, ECO:0000269|PubMed:21194680, ECO:0000269|PubMed:21750680, ECO:0000269|PubMed:23646827}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.131

Intolerance Scores

• loftool: 0.702
• rvis_EVS: 0.02
• rvis_percentile_EVS: 55.61

Haploinsufficiency Scores

• pHI: 0.328
• hipred: Y
• hipred_score: 0.614
• ghis: 0.449

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0867

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Smoc1
• 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); growth/size/body region phenotype; cellular phenotype; vision/eye phenotype; craniofacial 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); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); pigmentation phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; 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); limbs/digits/tail phenotype; digestive/alimentary phenotype

Zebrafish Information Network

• Gene name: smoc1
• Affected structure: optic fissure
• Phenotype tag: abnormal
• Phenotype quality: open

Gene ontology

• Biological process: eye development;cell differentiation;regulation of osteoblast differentiation;limb development
• Cellular component: basement membrane
• Molecular function: calcium ion binding;protein binding;extracellular matrix binding