Variant X-49030297-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_006521.6(TFE3):c.1589A>T(p.Glu530Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., 0 hem., cov: 11)

Exomes 𝑓: 0.000060 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

TFE3
NM_006521.6 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 2.93

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TFE3	NM_006521.6 linkuse as main transcript	c.1589A>T	p.Glu530Val	missense_variant	10/10	ENST00000315869.8	NP_006512.2
TFE3	NM_001282142.2 linkuse as main transcript	c.1274A>T	p.Glu425Val	missense_variant	10/10		NP_001269071.1
TFE3	XM_024452432.2 linkuse as main transcript	c.*219A>T		3_prime_UTR_variant	11/11		XP_024308200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFE3	ENST00000315869.8 linkuse as main transcript	c.1589A>T	p.Glu530Val	missense_variant	10/10	1	NM_006521.6	ENSP00000314129	P1	P19532-1
TFE3	ENST00000493583.5 linkuse as main transcript	c.*1194A>T		3_prime_UTR_variant, NMD_transcript_variant	10/10	2		ENSP00000476976		P19532-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

47392

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

11968

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000598

AC:

AN:

485343

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

151399

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000233

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000671

Gnomad4 OTH exome

AF:

0.0000566

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000211

AC:

AN:

47398

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

11980

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000576

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TFE3-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 22, 2023

The TFE3 c.1589A>T variant is predicted to result in the amino acid substitution p.Glu530Val. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.56

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.76

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.72

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.57

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.5

REVEL

Benign

0.16

Sift

Benign

0.043

Sift4G

Benign

0.15

Polyphen

0.97

Vest4

0.63

MutPred

0.39

Loss of solvent accessibility (P = 0.0224);

MVP

0.31

MPC

0.18

ClinPred

0.88

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.36

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over