LAMC3

laminin subunit gamma 3, the group of Laminin subunits

Basic information

Region (hg38): 9:131009174-131094473

Links

ENSG00000050555 ∙ NCBI:10319 ∙ OMIM:604349 ∙ HGNC:6494 ∙ Uniprot:Q9Y6N6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• occipital pachygyria and polymicrogyria (Definitive), mode of inheritance: AR
• occipital pachygyria and polymicrogyria (Moderate), mode of inheritance: AR
• occipital pachygyria and polymicrogyria (Supportive), mode of inheritance: AR
• occipital pachygyria and polymicrogyria (Definitive), mode of inheritance: AR
• occipital pachygyria and polymicrogyria (Strong), mode of inheritance: AR
• complex neurodevelopmental disorder (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cortical malformations, occipital	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	Neurologic	21572413

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LAMC3 gene.

• not provided (54 variants)
• Inborn genetic diseases (3 variants)
• Occipital pachygyria and polymicrogyria (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LAMC3 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	348	16	369
missense			628	26	15	669
nonsense	24	2	1			27
start loss						0
frameshift	31	7	3			41
inframe indel			10			10
splice donor/acceptor (+/-2bp)	1	22	2	1		26
splice region			22	46	2	70
non coding			5	207	101	313
Total	56	31	654	582	132

Highest pathogenic variant AF is 0.0000329

Variants in LAMC3

This is a list of pathogenic ClinVar variants found in the LAMC3 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-131009176-G-A		not specified	Likely benign (Jul 31, 2017)
9-131009213-C-T		not specified	Conflicting classifications of pathogenicity (Apr 18, 2018)
9-131009219-C-T		Occipital pachygyria and polymicrogyria	Uncertain significance (Nov 06, 2020)
9-131009228-C-T		Inborn genetic diseases	Uncertain significance (Sep 25, 2023)
9-131009240-GGCTGGCGCT-G			Uncertain significance (Nov 01, 2021)
9-131009241-G-T			Likely benign (Jan 15, 2024)
9-131009240-G-GGCTGGC			Uncertain significance (Jul 25, 2022)
9-131009253-G-A			Likely benign (Jan 10, 2024)
9-131009252-T-TGGCACCGCG		Occipital pachygyria and polymicrogyria	Conflicting classifications of pathogenicity (Jan 28, 2024)
9-131009256-A-C			Likely benign (Jun 27, 2022)
9-131009263-G-A			Uncertain significance (Aug 26, 2021)
9-131009266-G-T			Uncertain significance (Aug 05, 2021)
9-131009268-C-T			Likely benign (Sep 20, 2023)
9-131009272-G-T		Inborn genetic diseases	Uncertain significance (May 09, 2024)
9-131009273-C-T			Uncertain significance (Jun 01, 2023)
9-131009276-GC-G		Occipital pachygyria and polymicrogyria	Likely pathogenic (Oct 26, 2022)
9-131009277-C-A			Likely benign (Sep 03, 2023)
9-131009285-C-T		Inborn genetic diseases	Uncertain significance (Nov 27, 2023)
9-131009289-C-T		not specified	Benign (Feb 01, 2024)
9-131009306-G-T		not specified	Benign (Feb 01, 2024)
9-131009306-GC-TT			Uncertain significance (Feb 06, 2022)
9-131009310-G-T			Likely benign (Jan 22, 2024)
9-131009312-A-C		Inborn genetic diseases	Uncertain significance (Mar 16, 2022)
9-131009318-GC-G			Pathogenic (Feb 14, 2023)
9-131009319-C-T			Likely benign (Mar 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LAMC3	protein_coding	protein_coding	ENST00000361069	28	85392

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.37e-23	0.945	125446	0	302	125748	0.00120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.430	965	928	1.04	0.0000639	10124
Missense in Polyphen		307	324.64	0.94567		3694
Synonymous	-0.126	414	411	1.01	0.0000312	3163
Loss of Function	2.67	48	72.6	0.661	0.00000357	814

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000776	0.000774
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000708	0.000707
Finnish	0.00648	0.00649
European (Non-Finnish)	0.000832	0.000818
Middle Eastern	0.000708	0.000707
South Asian	0.000894	0.000882
Other	0.000990	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
• Disease: DISEASE: Cortical malformations occipital (OCCM) [MIM:614115]: A disease in which affected individuals develop seizures, sometimes associated with transient visual changes. Brain MRI shows both pachygyria and polymicrogyria restricted to the lateral occipital lobes. {ECO:0000269|PubMed:21572413}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);ECM-receptor interaction - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Signal Transduction;prion pathway;Laminin interactions;Extracellular matrix organization;agrin in postsynaptic differentiation;Non-integrin membrane-ECM interactions;MET activates PTK2 signaling;MET promotes cell motility;Signaling by MET;Signaling by Receptor Tyrosine Kinases (Consensus)

Intolerance Scores

• loftool: 0.837
• rvis_EVS: 0.64
• rvis_percentile_EVS: 83.64

Haploinsufficiency Scores

• pHI: 0.155
• hipred: Y
• hipred_score: 0.509
• ghis: 0.438

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.987

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lamc3
• Phenotype: skeleton phenotype; immune system phenotype; vision/eye 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); hematopoietic system phenotype

Zebrafish Information Network

• Gene name: lamc3
• Affected structure: primary motor neuron
• Phenotype tag: abnormal
• Phenotype quality: shape

Gene ontology

• Biological process: cell morphogenesis involved in differentiation;cell adhesion;visual perception;astrocyte development;extracellular matrix organization;retina development in camera-type eye
• Cellular component: extracellular region;basement membrane;membrane;extracellular matrix
• Molecular function: structural molecule activity