rs764899809

Variant names:

• chr15-70056320-C-A
• rs764899809
• NM_001105192.3:c.1306G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-70056320-C-A
• chr15-70056320-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001105192.3(TLE3):​c.1306G>T​(p.Ala436Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. A436T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TLE3 NM_001105192.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.865
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.082422644).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105192.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLE3	NM_001105192.3	MANE Select	c.1306G>T	p.Ala436Ser	missense	Exon 14 of 20	NP_001098662.1	Q04726-5
	TLE3	NM_001438147.1		c.1336G>T	p.Ala446Ser	missense	Exon 14 of 20	NP_001425076.1
	TLE3	NM_001438148.1		c.1321G>T	p.Ala441Ser	missense	Exon 14 of 20	NP_001425077.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLE3	ENST00000451782.7	TSL:5 MANE Select	c.1306G>T	p.Ala436Ser	missense	Exon 14 of 20	ENSP00000394717.3	Q04726-5
	TLE3	ENST00000558939.5	TSL:1	c.1315G>T	p.Ala439Ser	missense	Exon 14 of 20	ENSP00000452871.1	Q04726-1
	TLE3	ENST00000558379.5	TSL:1	c.1300G>T	p.Ala434Ser	missense	Exon 14 of 20	ENSP00000453435.1	Q04726-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Benign	0.80
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.18	N
PhyloP100		0.86
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.056
Sift	Benign	0.55	T
Sift4G	Benign	0.90	T
Polyphen		0.0010	B
Vest4		0.34
MutPred		0.47		Loss of sheet (P = 0.0025)
MVP		0.068
MPC		0.44
ClinPred		0.11	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.034
gMVP		0.21

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

Other links and lift over

dbSNP: rs764899809; hg19: chr15-70348659;