rs773096656

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001105192.3(TLE3):​c.1180C>T​(p.Pro394Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000373 in 1,607,274 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P394T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

TLE3
NM_001105192.3 missense

Scores

7
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.71
Variant links:
Genes affected
TLE3 (HGNC:11839): (TLE family member 3, transcriptional corepressor) This gene encodes a transcriptional co-repressor protein that belongs to the transducin-like enhancer family of proteins. The members of this family function in the Notch signaling pathway that regulates determination of cell fate during development. Expression of this gene has been associated with a favorable outcome to chemotherapy with taxanes for ovarian carcinoma. Alternate splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Sep 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.30842677).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TLE3NM_001105192.3 linkc.1180C>T p.Pro394Ser missense_variant Exon 13 of 20 ENST00000451782.7 NP_001098662.1 Q04726-5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TLE3ENST00000451782.7 linkc.1180C>T p.Pro394Ser missense_variant Exon 13 of 20 5 NM_001105192.3 ENSP00000394717.3 Q04726-5

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152278
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00000275
AC:
4
AN:
1454996
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
723252
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
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:
0.0000131
AC:
2
AN:
152278
Hom.:
0
Cov.:
34
AF XY:
0.0000134
AC XY:
1
AN XY:
74402
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
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:
0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.087
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.69
D;T;.;T;T;.;.;.;T;T;.;.;.;.
Eigen
Benign
0.039
Eigen_PC
Benign
0.14
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.92
D;D;D;D;D;D;D;.;D;D;D;D;D;D
M_CAP
Benign
0.059
D
MetaRNN
Benign
0.31
T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.77
T
MutationAssessor
Uncertain
2.4
M;.;.;.;.;.;.;.;.;.;.;.;M;.
PrimateAI
Uncertain
0.61
T
PROVEAN
Uncertain
-4.2
D;.;D;D;D;D;D;D;D;D;D;D;D;D
REVEL
Benign
0.11
Sift
Benign
0.038
D;.;T;D;D;D;T;T;D;D;D;T;D;T
Sift4G
Benign
0.10
T;T;T;D;T;T;T;T;T;T;T;T;T;T
Polyphen
0.0070
B;.;D;.;.;P;.;B;B;.;.;B;.;.
Vest4
0.27
MutPred
0.63
Loss of catalytic residue at P396 (P = 0.0096);Loss of catalytic residue at P396 (P = 0.0096);.;.;.;.;.;.;.;.;.;.;Loss of catalytic residue at P396 (P = 0.0096);.;
MVP
0.32
MPC
0.48
ClinPred
0.97
D
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.20
gMVP
0.45

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: rs773096656; hg19: chr15-70349869; API