Variant X-49030170-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006521.6(TFE3):c.1716A>G(p.Glu572=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000166 in 1,205,876 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 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 0.000018 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000016 ( 0 hom. 5 hem. )

Consequence

TFE3
NM_006521.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.507

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant X-49030170-T-C is Benign according to our data. Variant chrX-49030170-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 732446.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.507 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TFE3	NM_006521.6 linkuse as main transcript	c.1716A>G	p.Glu572=	synonymous_variant	10/10	ENST00000315869.8	NP_006512.2
TFE3	NM_001282142.2 linkuse as main transcript	c.1401A>G	p.Glu467=	synonymous_variant	10/10		NP_001269071.1
TFE3	XM_024452432.2 linkuse as main transcript	c.*346A>G		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.1716A>G	p.Glu572=	synonymous_variant	10/10	1	NM_006521.6	ENSP00000314129	P1	P19532-1
TFE3	ENST00000493583.5 linkuse as main transcript	c.*1321A>G		3_prime_UTR_variant, NMD_transcript_variant	10/10	2		ENSP00000476976		P19532-2

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111714

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33898

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000950

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000291

AC:

AN:

171937

Hom.:

AF XY:

0.0000171

AC XY:

AN XY:

58593

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000525

Gnomad OTH exome

AF:

0.000235

GnomAD4 exome

AF:

0.0000165

AC:

AN:

1094107

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

360139

show subpopulations

Gnomad4 AFR exome

AF:

0.0000760

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000952

Gnomad4 OTH exome

AF:

0.0000436

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111769

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

33963

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000949

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000480

Hom.:

Bravo

AF:

0.0000302

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 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

5.9

DANN

Benign

0.77

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