rs782080222
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3
The NM_006521.6(TFE3):c.1586_1591delAGGAGG(p.Glu529_Glu530del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000915 in 1,093,380 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 11)
Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )
Consequence
TFE3
NM_006521.6 disruptive_inframe_deletion
NM_006521.6 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.47
Publications
1 publications found
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 Gene-Disease associations (from GenCC):
- intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse faciesInheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
- X-linked syndromic complex neurodevelopmental disorderInheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
- complex neurodevelopmental disorderInheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_006521.6
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_006521.6. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TFE3 | NM_006521.6 | MANE Select | c.1586_1591delAGGAGG | p.Glu529_Glu530del | disruptive_inframe_deletion | Exon 10 of 10 | NP_006512.2 | ||
| TFE3 | NM_001282142.2 | c.1271_1276delAGGAGG | p.Glu424_Glu425del | disruptive_inframe_deletion | Exon 10 of 10 | NP_001269071.1 | B4DIA5 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TFE3 | ENST00000315869.8 | TSL:1 MANE Select | c.1586_1591delAGGAGG | p.Glu529_Glu530del | disruptive_inframe_deletion | Exon 10 of 10 | ENSP00000314129.7 | P19532-1 | |
| TFE3 | ENST00000874969.1 | c.1478_1483delAGGAGG | p.Glu493_Glu494del | disruptive_inframe_deletion | Exon 10 of 10 | ENSP00000545028.1 | |||
| TFE3 | ENST00000912302.1 | c.1400_1405delAGGAGG | p.Glu467_Glu468del | disruptive_inframe_deletion | Exon 10 of 10 | ENSP00000582361.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
11
GnomAD2 exomes AF: 0.00000559 AC: 1AN: 178943 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
178943
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 9.15e-7 AC: 1AN: 1093380Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 360714 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1093380
Hom.:
AF XY:
AC XY:
0
AN XY:
360714
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
26311
American (AMR)
AF:
AC:
0
AN:
34992
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19222
East Asian (EAS)
AF:
AC:
0
AN:
30139
South Asian (SAS)
AF:
AC:
0
AN:
53779
European-Finnish (FIN)
AF:
AC:
0
AN:
40421
Middle Eastern (MID)
AF:
AC:
0
AN:
4051
European-Non Finnish (NFE)
AF:
AC:
1
AN:
838580
Other (OTH)
AF:
AC:
0
AN:
45885
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
11
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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