rs758917874

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003200.5(TCF3):ā€‹c.1960A>Gā€‹(p.Met654Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

TCF3
NM_003200.5 missense

Scores

2
7
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.11
Variant links:
Genes affected
TCF3 (HGNC:11633): (transcription factor 3) This gene encodes a member of the E protein (class I) family of helix-loop-helix transcription factors. E proteins activate transcription by binding to regulatory E-box sequences on target genes as heterodimers or homodimers, and are inhibited by heterodimerization with inhibitor of DNA-binding (class IV) helix-loop-helix proteins. E proteins play a critical role in lymphopoiesis, and the encoded protein is required for B and T lymphocyte development. Deletion of this gene or diminished activity of the encoded protein may play a role in lymphoid malignancies. This gene is also involved in several chromosomal translocations that are associated with lymphoid malignancies including pre-B-cell acute lymphoblastic leukemia (t(1;19), with PBX1), childhood leukemia (t(19;19), with TFPT) and acute leukemia (t(12;19), with ZNF384). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the short arm of chromosome 9. [provided by RefSeq, Sep 2011]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26596364).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TCF3NM_003200.5 linkc.1960A>G p.Met654Val missense_variant Exon 19 of 19 ENST00000262965.12 NP_003191.1 P15923-1
TCF3NM_001136139.4 linkc.1951A>G p.Met651Val missense_variant Exon 19 of 20 ENST00000588136.7 NP_001129611.1 P15923-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TCF3ENST00000262965.12 linkc.1960A>G p.Met654Val missense_variant Exon 19 of 19 1 NM_003200.5 ENSP00000262965.5 P15923-1
TCF3ENST00000588136.7 linkc.1951A>G p.Met651Val missense_variant Exon 19 of 20 2 NM_001136139.4 ENSP00000468487.1 P15923-2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1460674
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
726598
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Uncertain
0.046
T
BayesDel_noAF
Benign
-0.17
CADD
Benign
13
DANN
Benign
0.87
DEOGEN2
Pathogenic
0.81
D;T;T;D;T;T;.;.;.
Eigen
Benign
-0.67
Eigen_PC
Benign
-0.69
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Pathogenic
0.98
D;D;D;.;D;D;D;D;D
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.27
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.3
M;.;.;M;.;.;.;.;.
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-2.8
D;.;.;.;.;.;.;.;D
REVEL
Benign
0.20
Sift
Uncertain
0.0020
D;.;.;.;.;.;.;.;D
Sift4G
Uncertain
0.0090
D;D;D;D;D;D;D;D;D
Polyphen
0.083
B;.;.;B;.;.;.;B;.
Vest4
0.33
MVP
0.32
MPC
0.040
ClinPred
0.67
D
GERP RS
-3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.48
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs758917874; hg19: chr19-1611711; API