rs151239650

Variant names:

• chr15-70053353-A-G
• rs151239650
• NM_001105192.3:c.1848T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001105192.3(TLE3):​c.1848T>C​(p.Asp616Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,608,182 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00057 (5 hom.)
• Consequence: TLE3 NM_001105192.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.71
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 15-70053353-A-G is Benign according to our data. Variant chr15-70053353-A-G is described in ClinVar as Benign. ClinVar VariationId is 720142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.71 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00533 (812/152242) while in subpopulation AFR AF = 0.0189 (787/41550). AF 95% confidence interval is 0.0178. There are 6 homozygotes in GnomAd4. There are 404 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 812 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.1848T>C	p.Asp616Asp	synonymous	Exon 17 of 20	NP_001098662.1	Q04726-5
	TLE3	NM_001438147.1		c.1878T>C	p.Asp626Asp	synonymous	Exon 17 of 20	NP_001425076.1
	TLE3	NM_001438148.1		c.1863T>C	p.Asp621Asp	synonymous	Exon 17 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.1848T>C	p.Asp616Asp	synonymous	Exon 17 of 20	ENSP00000394717.3	Q04726-5
	TLE3	ENST00000558939.5	TSL:1	c.1857T>C	p.Asp619Asp	synonymous	Exon 17 of 20	ENSP00000452871.1	Q04726-1
	TLE3	ENST00000558379.5	TSL:1	c.1842T>C	p.Asp614Asp	synonymous	Exon 17 of 20	ENSP00000453435.1	Q04726-6

Frequencies

GnomAD3 genomes AF: 0.00532 AC: 809 AN: 152124 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00135 AC: 322 AN: 239056 AF XY: 0.000981

Gnomad AFR exome AF: 0.0211

Gnomad AMR exome AF: 0.000448

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000461

Gnomad OTH exome AF: 0.000511

GnomAD4 exome AF: 0.000567 AC: 826 AN: 1455940 Hom.: 5 Cov.: 32 AF XY: 0.000480 AC XY: 347 AN XY: 723366

African (AFR) AF: 0.0214 AC: 713 AN: 33374

American (AMR) AF: 0.000545 AC: 24 AN: 44054

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25970

East Asian (EAS) AF: 0.00 AC: 0 AN: 39538

South Asian (SAS) AF: 0.0000470 AC: 4 AN: 85020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53018

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5756

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1109040

Other (OTH) AF: 0.00103 AC: 62 AN: 60170

GnomAD4 genome AF: 0.00533 AC: 812 AN: 152242 Hom.: 6 Cov.: 32 AF XY: 0.00543 AC XY: 404 AN XY: 74460

African (AFR) AF: 0.0189 AC: 787 AN: 41550

American (AMR) AF: 0.00105 AC: 16 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68002

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00272 Hom.: 1

Bravo AF: 0.00611

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.016
DANN	Benign	0.45
PhyloP100		-2.7
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs151239650; hg19: chr15-70345692;