Variant X-49030563-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_006521.6(TFE3):c.1323A>G(p.Val441=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 1,207,205 control chromosomes in the GnomAD database, including 93,853 homozygotes. There are 181,653 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.35 ( 6685 hom., 11158 hem., cov: 22)

Exomes 𝑓: 0.47 ( 87168 hom. 170495 hem. )

Consequence

TFE3
NM_006521.6 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.94

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant X-49030563-T-C is Benign according to our data. Variant chrX-49030563-T-C is described in ClinVar as [Benign]. Clinvar id is 3348548.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-49030563-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.94 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TFE3	NM_006521.6 linkuse as main transcript	c.1323A>G	p.Val441=	synonymous_variant	10/10	ENST00000315869.8	NP_006512.2
TFE3	XM_024452432.2 linkuse as main transcript	c.1369A>G	p.Thr457Ala	missense_variant	11/11		XP_024308200.1
TFE3	NM_001282142.2 linkuse as main transcript	c.1008A>G	p.Val336=	synonymous_variant	10/10		NP_001269071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFE3	ENST00000315869.8 linkuse as main transcript	c.1323A>G	p.Val441=	synonymous_variant	10/10	1	NM_006521.6	ENSP00000314129	P1	P19532-1
TFE3	ENST00000495940.2 linkuse as main transcript	n.710A>G		non_coding_transcript_exon_variant	2/2	2
TFE3	ENST00000493583.5 linkuse as main transcript	c.*928A>G		3_prime_UTR_variant, NMD_transcript_variant	10/10	2		ENSP00000476976		P19532-2

Frequencies

GnomAD3 genomes

AF:

0.355

AC:

39054

AN:

109926

Hom.:

6692

Cov.:

AF XY:

0.346

AC XY:

11147

AN XY:

32228

show subpopulations

Gnomad AFR

AF:

0.0722

Gnomad AMI

AF:

0.498

Gnomad AMR

AF:

0.324

Gnomad ASJ

AF:

0.587

Gnomad EAS

AF:

0.0830

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.458

Gnomad MID

AF:

0.645

Gnomad NFE

AF:

0.519

Gnomad OTH

AF:

0.410

GnomAD3 exomes

AF:

0.388

AC:

69795

AN:

179748

Hom.:

9875

AF XY:

0.405

AC XY:

26629

AN XY:

65810

show subpopulations

Gnomad AFR exome

AF:

0.0620

Gnomad AMR exome

AF:

0.278

Gnomad ASJ exome

AF:

0.583

Gnomad EAS exome

AF:

0.0802

Gnomad SAS exome

AF:

0.313

Gnomad FIN exome

AF:

0.465

Gnomad NFE exome

AF:

0.515

Gnomad OTH exome

AF:

0.450

GnomAD4 exome

AF:

0.472

AC:

518119

AN:

1097226

Hom.:

87168

Cov.:

AF XY:

0.470

AC XY:

170495

AN XY:

362720

show subpopulations

Gnomad4 AFR exome

AF:

0.0641

Gnomad4 AMR exome

AF:

0.283

Gnomad4 ASJ exome

AF:

0.582

Gnomad4 EAS exome

AF:

0.107

Gnomad4 SAS exome

AF:

0.320

Gnomad4 FIN exome

AF:

0.466

Gnomad4 NFE exome

AF:

0.515

Gnomad4 OTH exome

AF:

0.445

GnomAD4 genome

AF:

0.355

AC:

39040

AN:

109979

Hom.:

6685

Cov.:

AF XY:

0.346

AC XY:

11158

AN XY:

32291

show subpopulations

Gnomad4 AFR

AF:

0.0720

Gnomad4 AMR

AF:

0.323

Gnomad4 ASJ

AF:

0.587

Gnomad4 EAS

AF:

0.0835

Gnomad4 SAS

AF:

0.297

Gnomad4 FIN

AF:

0.458

Gnomad4 NFE

AF:

0.519

Gnomad4 OTH

AF:

0.407

Alfa

AF:

0.458

Hom.:

4895

Bravo

AF:

0.331

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TFE3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 15, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

1.9

DANN

Benign

0.70

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