IGSF3

immunoglobulin superfamily member 3, the group of V-set domain containing

Basic information

Region (hg38): 1:116574398-116667755

Links

ENSG00000143061 ∙ NCBI:3321 ∙ OMIM:603491 ∙ HGNC:5950 ∙ Uniprot:O75054 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial congenital nasolacrimal duct obstruction (Supportive), mode of inheritance: AR
• familial congenital nasolacrimal duct obstruction (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lacrimal duct defect	AR	Audiologic/Otolaryngologic	Awareness may allow early surgical treatemnt of nasolacrimal duct obstruction/dacryocystocele, which may be beneficial to avoid complications	Audiologic/Otolaryngologic	24372406

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IGSF3 gene.

• Inborn genetic diseases (55 variants)
• not provided (14 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IGSF3 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	2	7
missense			54	5	2	61
nonsense	1					1
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	1	1	54	10	4

Highest pathogenic variant AF is 0.000365

Variants in IGSF3

This is a list of pathogenic ClinVar variants found in the IGSF3 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-116577328-G-C		not specified	Uncertain significance (Dec 09, 2023)
1-116577443-G-A		not specified	Uncertain significance (Feb 22, 2023)
1-116577466-A-T		not specified	Uncertain significance (Oct 26, 2021)
1-116577470-T-C		not specified	Uncertain significance (Sep 29, 2022)
1-116577527-C-T		not specified	Uncertain significance (Apr 28, 2023)
1-116577532-T-C		not specified	Uncertain significance (Dec 20, 2023)
1-116579406-C-T		not specified	Likely benign (Sep 20, 2023)
1-116579407-G-A		not specified	Uncertain significance (Sep 20, 2023)
1-116579421-G-A		not specified	Uncertain significance (May 04, 2022)
1-116579426-C-G		not specified	Uncertain significance (Jun 05, 2023)
1-116579483-A-G		IGSF3-related disorder	Likely benign (Sep 17, 2019)
1-116579508-T-C		IGSF3-related disorder	Benign (Oct 21, 2019)
1-116579650-C-T		not specified	Uncertain significance (Jul 07, 2022)
1-116579656-C-CGTT		IGSF3-related disorder	Benign (Oct 07, 2019)
1-116579662-C-T		not specified	Uncertain significance (Dec 08, 2023)
1-116579662-CG-C			Likely pathogenic (Feb 26, 2020)
1-116579663-G-C		IGSF3-related disorder	Benign (Sep 26, 2019)
1-116579666-G-C		IGSF3-related disorder	Benign (Dec 31, 2019)
1-116579681-C-G		not specified	Uncertain significance (Feb 02, 2024)
1-116579710-G-C		not specified	Uncertain significance (Mar 13, 2023)
1-116579733-C-G		IGSF3-related disorder	Benign (Oct 02, 2019)
1-116579745-C-T		not specified	Uncertain significance (Apr 14, 2022)
1-116579767-C-A		not specified	Uncertain significance (Aug 12, 2022)
1-116579790-CG-C		Familial congenital nasolacrimal duct obstruction	Pathogenic (Dec 01, 2014)
1-116579844-T-C		not specified	Uncertain significance (Jul 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IGSF3	protein_coding	protein_coding	ENST00000369483	11	93345

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.265	0.735	125706	0	42	125748	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.77	631	769	0.820	0.0000497	7927
Missense in Polyphen		150	231.49	0.64798		2404
Synonymous	-1.23	353	325	1.09	0.0000222	2451
Loss of Function	5.34	13	56.1	0.232	0.00000319	530

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000590	0.000586
Ashkenazi Jewish	0.00	0.00
East Asian	0.000164	0.000163
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000215	0.000202
Middle Eastern	0.000164	0.000163
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Recessive Scores

• pRec: 0.125

Intolerance Scores

• loftool: 0.502
• rvis_EVS: -1.34
• rvis_percentile_EVS: 4.65

Haploinsufficiency Scores

• pHI: 0.558
• hipred: Y
• hipred_score: 0.575
• ghis: 0.604

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.353

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Igsf3

Gene ontology

• Biological process: lacrimal gland development
• Cellular component: cell surface;integral component of membrane
• Molecular function: molecular_function