rs782080222

Variant names:

• chrX-49030294-CCCTCCT-C
• rs782080222
• NM_006521.6:c.1586_1591delAGGAGG

Your query was ambiguous. Multiple possible variants found:

• chrX-49030294-CCCTCCT-C
• chrX-49030294-CCCTCCT-CCCT
• chrX-49030294-CCCTCCT-CCCTCCTCCT

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP3

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.47

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_006521.6

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFE3	NM_006521.6	c.1586_1591delAGGAGG	p.Glu529_Glu530del	disruptive_inframe_deletion	Exon 10 of 10	ENST00000315869.8	NP_006512.2
TFE3	NM_001282142.2	c.1271_1276delAGGAGG	p.Glu424_Glu425del	disruptive_inframe_deletion	Exon 10 of 10		NP_001269071.1
TFE3	XM_024452432.2	c.*216_*221delAGGAGG		3_prime_UTR_variant	Exon 11 of 11		XP_024308200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFE3	ENST00000315869.8	c.1586_1591delAGGAGG	p.Glu529_Glu530del	disruptive_inframe_deletion	Exon 10 of 10	1	NM_006521.6	ENSP00000314129.7
TFE3	ENST00000493583.5	n.*1191_*1196delAGGAGG		non_coding_transcript_exon_variant	Exon 10 of 10	2		ENSP00000476976.1
TFE3	ENST00000493583.5	n.*1191_*1196delAGGAGG		3_prime_UTR_variant	Exon 10 of 10	2		ENSP00000476976.1
TFE3	ENST00000495940.2	n.*215_*220delAGGAGG		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 11

GnomAD3 exomes AF: 0.00000559 AC: 1 AN: 178943 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 64665

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: 0.0000126

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.15e-7 AC: 1 AN: 1093380 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 360714

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: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 11

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs782080222; hg19: chrX-48887805;