chrX-49030466-C-T

Position:

chrX-49030466-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The ENST00000315869.8(TFE3):c.1420G>A(p.Ala474Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000827 in 1,209,519 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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: 22)

Exomes 𝑓: 0.0000073 ( 0 hom. 1 hem. )

Consequence

TFE3
ENST00000315869.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.59

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.032701045).

BP6

Variant X-49030466-C-T is Benign according to our data. Variant chrX-49030466-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2525671.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFE3	NM_006521.6 linkuse as main transcript	c.1420G>A	p.Ala474Thr	missense_variant	10/10	ENST00000315869.8	NP_006512.2	P19532-1A0A024QZ23
TFE3	NM_001282142.2 linkuse as main transcript	c.1105G>A	p.Ala369Thr	missense_variant	10/10		NP_001269071.1	P19532B4DIA5
TFE3	XM_024452432.2 linkuse as main transcript	c.*50G>A		3_prime_UTR_variant	11/11		XP_024308200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TFE3	ENST00000315869.8 linkuse as main transcript	c.1420G>A	p.Ala474Thr	missense_variant	10/10	1	NM_006521.6	ENSP00000314129.7	P19532-1
TFE3	ENST00000493583.5 linkuse as main transcript	n.*1025G>A		non_coding_transcript_exon_variant	10/10	2		ENSP00000476976.1	P19532-2
TFE3	ENST00000493583.5 linkuse as main transcript	n.*1025G>A		3_prime_UTR_variant	10/10	2		ENSP00000476976.1	P19532-2
TFE3	ENST00000495940.2 linkuse as main transcript	n.*49G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

111311

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33511

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000378

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000110

AC:

AN:

181720

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67328

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:

0.0000249

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000728

AC:

AN:

1098208

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363578

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000831

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000180

AC:

AN:

111311

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33511

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:

0.00

Gnomad4 NFE

AF:

0.0000378

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-1.2

CADD

Benign

0.0060

DANN

Benign

0.96

DEOGEN2

Benign

0.32

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.52

M_CAP

Benign

0.0037

MetaRNN

Benign

0.033

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.42

PROVEAN

Benign

0.31

REVEL

Benign

0.0020

Sift

Benign

0.99

Sift4G

Benign

0.80

Polyphen

0.0

Vest4

0.050

MVP

0.068

MPC

0.19

ClinPred

0.12

GERP RS

-4.4

Varity_R

0.046

gMVP

0.23

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