rs759781735

Variant names:

• chr15-70057655-G-A
• rs759781735
• NM_001105192.3:c.1055C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-70057655-G-A
• chr15-70057655-G-C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.43
• Publications: 2 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16114971).
• BS2: High AC in GnomAdExome4 at 16 AD gene.

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.1055C>T	p.Ser352Leu	missense	Exon 13 of 20	NP_001098662.1	Q04726-5
	TLE3	NM_001438147.1		c.1085C>T	p.Ser362Leu	missense	Exon 13 of 20	NP_001425076.1
	TLE3	NM_001438148.1		c.1085C>T	p.Ser362Leu	missense	Exon 13 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.1055C>T	p.Ser352Leu	missense	Exon 13 of 20	ENSP00000394717.3	Q04726-5
	TLE3	ENST00000558939.5	TSL:1	c.1064C>T	p.Ser355Leu	missense	Exon 13 of 20	ENSP00000452871.1	Q04726-1
	TLE3	ENST00000558379.5	TSL:1	c.1064C>T	p.Ser355Leu	missense	Exon 13 of 20	ENSP00000453435.1	Q04726-6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000276 AC: 5 AN: 180942 AF XY: 0.0000307

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000246

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000113 AC: 16 AN: 1416104 Hom.: 0 Cov.: 33 AF XY: 0.00000856 AC XY: 6 AN XY: 701338

African (AFR) AF: 0.00 AC: 0 AN: 32860

American (AMR) AF: 0.000206 AC: 8 AN: 38822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25522

East Asian (EAS) AF: 0.00 AC: 0 AN: 37968

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4782

European-Non Finnish (NFE) AF: 0.00000548 AC: 6 AN: 1094988

Other (OTH) AF: 0.0000169 AC: 1 AN: 59014

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000251 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.094
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.53	N
PhyloP100		9.4
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.10
Sift	Benign	0.31	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.53
MutPred		0.44		Gain of catalytic residue at S355 (P = 0.0196)
MVP		0.15
MPC		0.45
ClinPred		0.22	T
GERP RS		5.4
Varity_R		0.077
gMVP		0.46
Mutation Taster		=45/55	disease causing

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

Other links and lift over

dbSNP: rs759781735; hg19: chr15-70349994;