TCF20

transcription factor 20

Basic information

Region (hg38): 22:42160013-42343616

Links

ENSG00000100207 ∙ NCBI:6942 ∙ OMIM:603107 ∙ HGNC:11631 ∙ Uniprot:Q9UGU0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental delay with variable intellectual impairment and behavioral abnormalities (Strong), mode of inheritance: AD
• developmental delay with variable intellectual impairment and behavioral abnormalities (Strong), mode of inheritance: AD
• syndromic intellectual disability (Supportive), mode of inheritance: AD
• developmental delay with variable intellectual impairment and behavioral abnormalities (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental delay with variable intellectual impairment and behavioral abnormalities	AD	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	Craniofacial; Musculoskeletal; Neurologic	25228304; 27436265; 28135719; 30739909; 30819258

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TCF20 gene.

• not provided (36 variants)
• Developmental delay with variable intellectual impairment and behavioral abnormalities (30 variants)
• Neurodevelopmental abnormality (13 variants)
• Inborn genetic diseases (7 variants)
• Neurodevelopmental delay (2 variants)
• See cases (2 variants)
• TCF20-related disorder (1 variants)
• Global developmental delay (1 variants)
• Failure to thrive;Pectus excavatum;Intellectual disability, moderate;Generalized hypotonia;Ptosis (1 variants)
• Autism;Intellectual disability, mild;Myoclonus (1 variants)
• Autism spectrum disorder (1 variants)
• Intellectual disability (1 variants)
• Autism;Intellectual disability, mild (1 variants)
• Craniosynostosis syndrome (1 variants)
• Autistic behavior;Attention deficit hyperactivity disorder;Hypotonia;Neurodevelopmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TCF20 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			3	198	28	229
missense	1	2	425	81	30	539
nonsense	28	7				35
start loss						0
frameshift	44	15	1			60
inframe indel			19	7	2	28
splice donor/acceptor (+/-2bp)						0
splice region			1	4		5
non coding			2	6	2	10
Total	73	24	450	292	62

Variants in TCF20

This is a list of pathogenic ClinVar variants found in the TCF20 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-42168597-G-GC		Developmental delay with variable intellectual impairment and behavioral abnormalities	Uncertain significance (Sep 22, 2024)
22-42168601-C-T		Developmental delay with variable intellectual impairment and behavioral abnormalities	Uncertain significance (Apr 14, 2020)
22-42168651-C-A		TCF20-related disorder	Likely benign (Feb 18, 2024)
22-42168660-C-T		Inborn genetic diseases	Likely benign (Jul 06, 2021)
22-42168661-G-A		Inborn genetic diseases	Likely benign (Nov 09, 2024)
22-42168679-T-A			Conflicting classifications of pathogenicity (Oct 01, 2024)
22-42168692-C-T			Likely benign (Apr 05, 2024)
22-42168693-G-C			Likely benign (Nov 03, 2024)
22-42168694-C-A		Inborn genetic diseases	Uncertain significance (Apr 28, 2021)
22-42168694-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Mar 16, 2024)
22-42168695-G-A			Likely benign (Oct 27, 2024)
22-42168695-G-C			Likely benign (Nov 24, 2023)
22-42168700-T-C			Uncertain significance (May 01, 2023)
22-42168709-AGG-A			Uncertain significance (Feb 01, 2023)
22-42168710-G-C			Likely benign (Jan 01, 2025)
22-42168711-G-A			Uncertain significance (Oct 15, 2024)
22-42168711-G-C			Benign (Dec 28, 2024)
22-42168711-G-T		TCF20-related disorder	Benign (Dec 28, 2024)
22-42168712-G-A			Benign (Dec 22, 2024)
22-42168712-G-C		TCF20-related disorder	Benign (Dec 28, 2024)
22-42168712-G-T			Benign/Likely benign (Oct 25, 2024)
22-42168713-G-C			Likely benign (Dec 18, 2024)
22-42168718-G-C		Inborn genetic diseases	Conflicting classifications of pathogenicity (Oct 13, 2023)
22-42168726-G-A			Benign (Sep 05, 2024)
22-42168726-G-T		Developmental delay with variable intellectual impairment and behavioral abnormalities	Uncertain significance (Dec 19, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TCF20	protein_coding	protein_coding	ENST00000359486	4	183604

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	7.98e-10	125741	0	4	125745	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0895	1048	1.06e+3	0.992	0.0000594	12835
Missense in Polyphen		331	409.88	0.80755		5106
Synonymous	-3.14	490	409	1.20	0.0000235	3975
Loss of Function	7.32	2	66.4	0.0301	0.00000368	795

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000553	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000176
Middle Eastern	0.0000553	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional activator that binds to the regulatory region of MMP3 and thereby controls stromelysin expression. It stimulates the activity of various transcriptional activators such as JUN, SP1, PAX6 and ETS1, suggesting a function as a coactivator.
• Pathway: Matrix Metalloproteinases (Consensus)

Recessive Scores

• pRec: 0.194

Intolerance Scores

• loftool: 0.0597
• rvis_EVS: -2.55
• rvis_percentile_EVS: 0.85

Haploinsufficiency Scores

• pHI: 0.332
• hipred: N
• hipred_score: 0.380
• ghis: 0.558

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.602

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tcf20

Gene ontology

• Biological process: regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus;nucleoplasm;nuclear body
• Molecular function: DNA binding;DNA-binding transcription factor activity;transcription coactivator activity;RNA binding;protein binding;transcription regulatory region DNA binding;metal ion binding