rs369167598

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_024760.3(TLE6):c.-53C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,613,100 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: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

TLE6
NM_024760.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.32

Publications

2 publications found

Variant links:

Genes affected

TLE6 (HGNC:30788): (TLE family member 6, subcortical maternal complex member) This gene encodes a member of the Groucho/ transducin-like Enhancer of split family of transcriptional co-repressors. The encoded protein is a component of the mammalian subcortical maternal complex, which is required for preimplantation development. In mouse, knock out of this gene results in cleavage-stage embryonic arrest resulting from defective cytoplasmic F-actin meshwork formation and asymmetric cell division. In human, an allelic variant in this gene is associated with preimplantation embryonic lethality. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

TLE6 Gene-Disease associations (from GenCC):

preimplantation embryonic lethality 1
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia

TLE6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012598127).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000256 (39/152128) while in subpopulation NFE AF = 0.000323 (22/68032). AF 95% confidence interval is 0.000218. There are 0 homozygotes in GnomAd4. There are 14 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024760.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TLE6	NM_001143986.2	MANE Select	c.317C>T	p.Thr106Met	missense	Exon 7 of 17	NP_001137458.1	Q9H808-1
TLE6	NM_024760.3		c.-53C>T		5_prime_UTR_premature_start_codon_gain	Exon 6 of 16	NP_079036.1	Q9H808-2
TLE6	NM_024760.3		c.-53C>T		5_prime_UTR	Exon 6 of 16	NP_079036.1	Q9H808-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TLE6	ENST00000452088.5	TSL:1	c.-53C>T		5_prime_UTR_premature_start_codon_gain	Exon 6 of 16	ENSP00000406893.1	Q9H808-2
TLE6	ENST00000246112.9	TSL:1 MANE Select	c.317C>T	p.Thr106Met	missense	Exon 7 of 17	ENSP00000246112.3	Q9H808-1
TLE6	ENST00000452088.5	TSL:1	c.-53C>T		5_prime_UTR	Exon 6 of 16	ENSP00000406893.1	Q9H808-2

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000200

AC:

AN:

249944

AF XY:

0.000170

show subpopulations

Gnomad AFR exome

AF:

0.0000623

Gnomad AMR exome

AF:

0.000493

Gnomad ASJ exome

AF:

0.00150

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000131

AC:

192

AN:

1460972

Hom.:

Cov.:

AF XY:

0.000131

AC XY:

AN XY:

726644

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33462

American (AMR)

AF:

0.000515

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00153

AC:

AN:

26088

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000954

AC:

106

AN:

1111334

Other (OTH)

AF:

0.000298

AC:

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000256

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41444

American (AMR)

AF:

0.000131

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000323

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000429

Hom.:

Bravo

AF:

0.000230

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000629

AC:

ExAC

AF:

0.000173

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.46

M_CAP

Benign

0.0039

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

-1.3

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.5

REVEL

Benign

0.024

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.033

Vest4

0.097

MVP

0.014

MPC

0.066

ClinPred

0.025

GERP RS

-2.0

Varity_R

0.024

gMVP

0.052

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over