Haematological malignancies cancer susceptibility

Gene: TCF3

Amber List (moderate evidence)

TCF3 (transcription factor 3)
EnsemblGeneIds (GRCh38): ENSG00000071564
EnsemblGeneIds (GRCh37): ENSG00000071564
OMIM: 147141, Gene2Phenotype
TCF3 is in 3 panels

3 reviews

Arina Puzriakova (Genomics England Curator)

I don't know

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. Additional comments from reviewing GLHs: no clinical guidelines to manage the findings.
Created: 12 Mar 2026, 9:51 a.m. | Last Modified: 12 Mar 2026, 9:51 a.m.
Panel Version: 4.39
Comment on mode of inheritance: Updated MOI to monoallelic - PMID: 36576946 states that 'The allele fraction of each variant in each sample was confirmed to be ∼50%, consistent with a heterozygous genotype.'
Created: 30 Oct 2025, 2:22 p.m. | Last Modified: 30 Oct 2025, 2:22 p.m.
Panel Version: 4.35

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

PMID: 36576946 report twelve rare germline TCF3 variants in patients with B-cell acute lymphoblastic leukemia (B-ALL). The authors regard these variants as deleterious, and 6/7 variants tested significantly reduced expression in luciferase assays (PMID: 36576946). Additional rare deleterious germlineTCF3 variants have been reported in B-ALL patients (PMID: 37129918), leading to the hypothesis that such variants may contribute to B-ALL susceptibility.
Created: 7 May 2025, 2:06 p.m. | Last Modified: 7 May 2025, 2:06 p.m.
Panel Version: 4.8

Phenotypes
B-cell acute lymphoblastic leukemia, MONDO:0004947

Lauma Freimane (Children's Clinical University Hospital)

Green List (high evidence)

Autors hypothesize that variants in TCF3 gene alter B-cell maturation which may increase the risk for preleukemic clone emergence (PMID: 36576946).
Sources: Literature
Created: 12 Jun 2023, 2:11 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
B-cell acute lymphoblastic leukemia

Publications

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
Phenotypes
  • B-cell acute lymphoblastic leukemia, MONDO:0004947
OMIM
147141
Clinvar variants
Variants in TCF3
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

12 Mar 2026, Gel status: 2

Removed Tag, Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_25_ promote_green was removed from gene: TCF3. Tag Q2_25_expert_review was removed from gene: TCF3.

30 Oct 2025, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: TCF3 were changed from B-cell acute lymphoblastic leukemia to B-cell acute lymphoblastic leukemia, MONDO:0004947

30 Oct 2025, Gel status: 2

Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

Mode of inheritance for gene: TCF3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

7 May 2025, Gel status: 2

Added Tag, Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q2_25_ promote_green tag was added to gene: TCF3. Tag Q2_25_expert_review tag was added to gene: TCF3.

1 May 2025, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: TCF3 were set to 36576946

1 May 2025, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: tcf3 has been classified as Amber List (Moderate Evidence).

12 Jun 2023, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Lauma Freimane (Children's Clinical University Hospital)

gene: TCF3 was added gene: TCF3 was added to Haematological malignancies cancer susceptibility. Sources: Literature Mode of inheritance for gene: TCF3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: TCF3 were set to 36576946 Phenotypes for gene: TCF3 were set to B-cell acute lymphoblastic leukemia Penetrance for gene: TCF3 were set to unknown Review for gene: TCF3 was set to GREEN gene: TCF3 was marked as current diagnostic