Variant 15-70057655-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001105192.3(TLE3):c.1055C>T(p.Ser352Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,416,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

TLE3
NM_001105192.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.43

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]

TLE3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16114971).

BS2

High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLE3	NM_001105192.3 link	c.1055C>T	p.Ser352Leu	missense_variant	13/20	ENST00000451782.7	NP_001098662.1	Q04726-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLE3	ENST00000451782.7 link	c.1055C>T	p.Ser352Leu	missense_variant	13/20	5	NM_001105192.3	ENSP00000394717.3		Q04726-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000276

AC:

AN:

180942

Hom.:

AF XY:

0.0000307

AC XY:

AN XY:

97764

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000109

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000246

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000113

AC:

AN:

1416104

Hom.:

Cov.:

AF XY:

0.00000856

AC XY:

AN XY:

701338

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000206

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000548

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000251

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.1064C>T (p.S355L) alteration is located in exon 13 (coding exon 13) of the TLE3 gene. This alteration results from a C to T substitution at nucleotide position 1064, causing the serine (S) at amino acid position 355 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.047

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;T;.;T;T;.;.;.;T;T;.;.;.;.

Eigen

Benign

-0.14

Eigen_PC

Benign

0.094

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;D;D;D;D;D;.;D;D;D;D;D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.16

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.53

N;.;.;.;.;.;.;.;.;.;.;.;N;.

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.4

N;.;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.31

T;.;T;T;T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.30

T;T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.0

B;.;B;.;.;B;.;B;B;.;.;B;.;.

Vest4

0.53

MutPred

0.44

Gain of catalytic residue at S355 (P = 0.0196);Gain of catalytic residue at S355 (P = 0.0196);.;.;.;.;.;.;.;.;.;.;Gain of catalytic residue at S355 (P = 0.0196);.;

MVP

0.15

MPC

0.45

ClinPred

0.22

GERP RS

5.4

Varity_R

0.077

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over