Variant X-49030447-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006521.6(TFE3):c.1439G>T(p.Gly480Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000278 in 1,209,577 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 119 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.00029 ( 0 hom. 117 hem. )

Consequence

TFE3
NM_006521.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.50

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02219832).

BP6

Variant X-49030447-C-A is Benign according to our data. Variant chrX-49030447-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 749357.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TFE3	NM_006521.6 linkuse as main transcript	c.1439G>T	p.Gly480Val	missense_variant	10/10	ENST00000315869.8	NP_006512.2
TFE3	NM_001282142.2 linkuse as main transcript	c.1124G>T	p.Gly375Val	missense_variant	10/10		NP_001269071.1
TFE3	XM_024452432.2 linkuse as main transcript	c.*69G>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.1439G>T	p.Gly480Val	missense_variant	10/10	1	NM_006521.6	ENSP00000314129	P1	P19532-1
TFE3	ENST00000493583.5 linkuse as main transcript	c.*1044G>T		3_prime_UTR_variant, NMD_transcript_variant	10/10	2		ENSP00000476976		P19532-2

Frequencies

GnomAD3 genomes

AF:

0.000153

AC:

AN:

111289

Hom.:

Cov.:

AF XY:

0.0000597

AC XY:

AN XY:

33479

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000331

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000283

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000247

AC:

AN:

182112

Hom.:

AF XY:

0.000149

AC XY:

AN XY:

67316

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.000999

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000290

AC:

319

AN:

1098236

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

117

AN XY:

363604

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.000111

Gnomad4 FIN exome

AF:

0.00113

Gnomad4 NFE exome

AF:

0.000280

Gnomad4 OTH exome

AF:

0.000499

GnomAD4 genome

AF:

0.000153

AC:

AN:

111341

Hom.:

Cov.:

AF XY:

0.0000596

AC XY:

AN XY:

33541

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000331

Gnomad4 NFE

AF:

0.000283

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000437

Hom.:

Bravo

AF:

0.000136

ExAC

AF:

0.000206

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

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

Labcorp Genetics (formerly Invitae), Labcorp

Jul 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.058

DANN

Benign

0.72

DEOGEN2

Uncertain

0.52

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.50

M_CAP

Benign

0.0029

MetaRNN

Benign

0.022

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.46

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.92

REVEL

Benign

0.030

Sift

Uncertain

0.021

Sift4G

Benign

0.13

Polyphen

0.0

Vest4

0.22

MVP

0.043

MPC

0.039

ClinPred

0.025

GERP RS

-7.9

Varity_R

0.085

gMVP

0.38

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