X-49030294-CCCTCCT-CCCT

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2

The NM_006521.6(TFE3):c.1589_1591delAGG(p.Glu530del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000635 in 1,201,310 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 232 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., 6 hem., cov: 11)

Exomes 𝑓: 0.00066 ( 0 hom. 226 hem. )

Consequence

TFE3
NM_006521.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.93

Publications

1 publications found

Variant links:

Genes affected

TFE3 (HGNC:11752): (transcription factor binding to IGHM enhancer 3) This gene encodes a basic helix-loop-helix domain-containing transcription factor that binds MUE3-type E-box sequences in the promoter of genes. The encoded protein promotes the expression of genes downstream of transforming growth factor beta (TGF-beta) signaling. This gene may be involved in chromosomal translocations in renal cell carcinomas and other cancers, resulting in the production of fusion proteins. Translocation partners include PRCC (papillary renal cell carcinoma), NONO (non-POU domain containing, octamer-binding), and ASPSCR1 (alveolar soft part sarcoma chromosome region, candidate 1), among other genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

TFE3 Gene-Disease associations (from GenCC):

intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
X-linked syndromic complex neurodevelopmental disorder
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
complex neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

TFE3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_006521.6

BP6

Variant X-49030294-CCCT-C is Benign according to our data. Variant chrX-49030294-CCCT-C is described in ClinVar as Benign. ClinVar VariationId is 3176514.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 37 XL,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006521.6. 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
	TFE3	NM_006521.6	MANE Select	c.1589_1591delAGG	p.Glu530del	disruptive_inframe_deletion	Exon 10 of 10	NP_006512.2
	TFE3	NM_001282142.2		c.1274_1276delAGG	p.Glu425del	disruptive_inframe_deletion	Exon 10 of 10	NP_001269071.1	B4DIA5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TFE3	ENST00000315869.8	TSL:1 MANE Select	c.1589_1591delAGG	p.Glu530del	disruptive_inframe_deletion	Exon 10 of 10	ENSP00000314129.7	P19532-1
TFE3	ENST00000874969.1		c.1481_1483delAGG	p.Glu494del	disruptive_inframe_deletion	Exon 10 of 10	ENSP00000545028.1
TFE3	ENST00000912302.1		c.1403_1405delAGG	p.Glu468del	disruptive_inframe_deletion	Exon 10 of 10	ENSP00000582361.1

Frequencies

GnomAD3 genomes

AF:

0.000339

AC:

AN:

109189

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000666

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000633

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000173

AC:

AN:

178943

AF XY:

0.000139

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000148

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000190

Gnomad NFE exome

AF:

0.000290

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

AF:

0.000665

AC:

726

AN:

1092070

Hom.:

AF XY:

0.000628

AC XY:

226

AN XY:

359926

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26289

American (AMR)

AF:

0.000143

AC:

AN:

34967

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19213

East Asian (EAS)

AF:

0.00

AC:

AN:

30127

South Asian (SAS)

AF:

0.00

AC:

AN:

53724

European-Finnish (FIN)

AF:

0.000124

AC:

AN:

40409

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4048

European-Non Finnish (NFE)

AF:

0.000835

AC:

699

AN:

837486

Other (OTH)

AF:

0.000371

AC:

AN:

45807

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

108

135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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:

0.000339

AC:

AN:

109240

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

AN XY:

31570

show subpopulations

African (AFR)

AF:

0.0000664

AC:

AN:

30104

American (AMR)

AF:

0.000196

AC:

AN:

10207

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2627

East Asian (EAS)

AF:

0.00

AC:

AN:

3437

South Asian (SAS)

AF:

0.00

AC:

AN:

2482

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5935

Middle Eastern (MID)

AF:

0.00

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.000634

AC:

AN:

52088

Other (OTH)

AF:

0.00

AC:

AN:

1481

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000800

Hom.:

Bravo

AF:

0.000332

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.9

Mutation Taster

=76/24

polymorphism

(source)

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

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