19-1611742-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003200.5(TCF3):ā€‹c.1930C>Gā€‹(p.Leu644Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 30)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

TCF3
NM_003200.5 missense

Scores

6
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.60
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23547953).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TCF3NM_003200.5 linkc.1930C>G p.Leu644Val missense_variant Exon 19 of 19 ENST00000262965.12 NP_003191.1 P15923-1
TCF3NM_001136139.4 linkc.1921C>G p.Leu641Val 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.1930C>G p.Leu644Val missense_variant Exon 19 of 19 1 NM_003200.5 ENSP00000262965.5 P15923-1
TCF3ENST00000588136.7 linkc.1921C>G p.Leu641Val missense_variant Exon 19 of 20 2 NM_001136139.4 ENSP00000468487.1 P15923-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152114
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461588
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727098
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152114
Hom.:
0
Cov.:
30
AF XY:
0.0000135
AC XY:
1
AN XY:
74300
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Uncertain
0.068
T
BayesDel_noAF
Benign
-0.14
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.45
T;T;T;T;T;T;.;.;.
Eigen
Uncertain
0.23
Eigen_PC
Benign
0.19
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.85
T;T;T;.;T;T;D;T;T
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.24
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.53
T
MutationAssessor
Benign
1.2
L;.;.;L;.;.;.;.;.
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-2.0
N;.;.;.;.;.;.;.;N
REVEL
Benign
0.12
Sift
Benign
0.063
T;.;.;.;.;.;.;.;T
Sift4G
Uncertain
0.032
D;D;T;D;D;T;T;D;D
Polyphen
1.0
D;.;.;D;.;.;.;D;.
Vest4
0.31
MutPred
0.20
.;.;.;.;.;.;.;.;Gain of glycosylation at S649 (P = 0.1017);
MVP
0.51
MPC
0.27
ClinPred
0.70
D
GERP RS
3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.086
gMVP
0.40

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs867262873; hg19: chr19-1611741; API