9-79652729-T-A

Variant summary

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

The NM_007005.6(TLE4):​c.527T>A​(p.Leu176Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TLE4
NM_007005.6 missense

Scores

1
11
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.82
Variant links:
Genes affected
TLE4 (HGNC:11840): (TLE family member 4, transcriptional corepressor) Predicted to enable transcription corepressor activity. Predicted to be involved in negative regulation of canonical Wnt signaling pathway. Predicted to act upstream of or within Wnt signaling pathway; cellular response to leukemia inhibitory factor; and negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of beta-catenin-TCF complex. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.38785267).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TLE4NM_007005.6 linkuse as main transcriptc.527T>A p.Leu176Gln missense_variant 7/20 ENST00000376552.8 NP_008936.2 Q04727-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TLE4ENST00000376552.8 linkuse as main transcriptc.527T>A p.Leu176Gln missense_variant 7/201 NM_007005.6 ENSP00000365735.2 Q04727-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsApr 13, 2023The c.527T>A (p.L176Q) alteration is located in exon 7 (coding exon 7) of the TLE4 gene. This alteration results from a T to A substitution at nucleotide position 527, causing the leucine (L) at amino acid position 176 to be replaced by a glutamine (Q). 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
Uncertain
0.46
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.39
T;.;T;.;.;T;T;T
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.90
D;D;D;D;D;D;D;D
M_CAP
Benign
0.060
D
MetaRNN
Benign
0.39
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.33
T
MutationAssessor
Uncertain
2.6
M;M;.;M;.;.;.;.
PrimateAI
Uncertain
0.74
T
PROVEAN
Uncertain
-2.9
D;D;D;D;D;D;D;D
REVEL
Benign
0.18
Sift
Benign
0.040
D;D;D;D;D;D;D;D
Sift4G
Uncertain
0.055
T;T;D;T;D;D;D;D
Polyphen
0.36
B;P;.;D;.;.;.;.
Vest4
0.80
MutPred
0.25
Loss of stability (P = 0.0254);Loss of stability (P = 0.0254);.;Loss of stability (P = 0.0254);.;.;.;.;
MVP
0.20
MPC
0.76
ClinPred
0.96
D
GERP RS
6.0
Varity_R
0.36
gMVP
0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-82267644; API