Variant X-49030524-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000315869.8(TFE3):c.1362G>A(p.Ser454Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00026 in 1,209,705 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 113 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., 10 hem., cov: 22)

Exomes 𝑓: 0.00026 ( 0 hom. 103 hem. )

Consequence

TFE3
ENST00000315869.8 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.59

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 links:

TFE3 (HGNC:):

TFE3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant X-49030524-C-T is Benign according to our data. Variant chrX-49030524-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2660499.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.59 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFE3	NM_006521.6 linkuse as main transcript	c.1362G>A	p.Ser454Ser	synonymous_variant	10/10	ENST00000315869.8	NP_006512.2	P19532-1A0A024QZ23
TFE3	XM_024452432.2 linkuse as main transcript	c.1408G>A	p.Gly470Ser	missense_variant	11/11		XP_024308200.1
TFE3	NM_001282142.2 linkuse as main transcript	c.1047G>A	p.Ser349Ser	synonymous_variant	10/10		NP_001269071.1	P19532B4DIA5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TFE3	ENST00000315869.8 linkuse as main transcript	c.1362G>A	p.Ser454Ser	synonymous_variant	10/10	1	NM_006521.6	ENSP00000314129.7	P19532-1
TFE3	ENST00000493583.5 linkuse as main transcript	n.*967G>A		non_coding_transcript_exon_variant	10/10	2		ENSP00000476976.1	P19532-2
TFE3	ENST00000495940.2 linkuse as main transcript	n.749G>A		non_coding_transcript_exon_variant	2/2	2
TFE3	ENST00000493583.5 linkuse as main transcript	n.*967G>A		3_prime_UTR_variant	10/10	2		ENSP00000476976.1	P19532-2

Frequencies

GnomAD3 genomes

AF:

0.000224

AC:

AN:

111456

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

AN XY:

33646

show subpopulations

Gnomad AFR

AF:

0.0000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000372

Gnomad FIN

AF:

0.00116

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000283

Gnomad OTH

AF:

0.000671

GnomAD3 exomes

AF:

0.000320

AC:

AN:

181452

Hom.:

AF XY:

0.000416

AC XY:

AN XY:

67228

show subpopulations

Gnomad AFR exome

AF:

0.0000761

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000524

Gnomad FIN exome

AF:

0.000750

Gnomad NFE exome

AF:

0.000413

Gnomad OTH exome

AF:

0.000442

GnomAD4 exome

AF:

0.000264

AC:

290

AN:

1098197

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

103

AN XY:

363567

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000554

Gnomad4 FIN exome

AF:

0.00118

Gnomad4 NFE exome

AF:

0.000235

Gnomad4 OTH exome

AF:

0.000304

GnomAD4 genome

AF:

0.000224

AC:

AN:

111508

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

AN XY:

33708

show subpopulations

Gnomad4 AFR

AF:

0.0000325

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000373

Gnomad4 FIN

AF:

0.00116

Gnomad4 NFE

AF:

0.000283

Gnomad4 OTH

AF:

0.000662

Alfa

AF:

0.000216

Hom.:

Bravo

AF:

0.000136

EpiCase

AF:

0.000327

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

TFE3: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.068

DANN

Benign

0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over