X-49030359-G-A

Variant names:

• chrX-49030359-G-A
• rs2064692276
• NM_006521.6:c.1527C>T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_006521.6(TFE3):​c.1527C>T​(p.His509His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 21)
• Consequence: TFE3 NM_006521.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.290

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant X-49030359-G-A is Benign according to our data. Variant chrX-49030359-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3772426.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.29 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFE3	NM_006521.6	c.1527C>T	p.His509His	synonymous_variant	Exon 10 of 10	ENST00000315869.8	NP_006512.2
TFE3	NM_001282142.2	c.1212C>T	p.His404His	synonymous_variant	Exon 10 of 10		NP_001269071.1
TFE3	XM_024452432.2	c.*157C>T		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.1527C>T	p.His509His	synonymous_variant	Exon 10 of 10	1	NM_006521.6	ENSP00000314129.7
TFE3	ENST00000493583.5	n.*1132C>T		non_coding_transcript_exon_variant	Exon 10 of 10	2		ENSP00000476976.1
TFE3	ENST00000493583.5	n.*1132C>T		3_prime_UTR_variant	Exon 10 of 10	2		ENSP00000476976.1
TFE3	ENST00000495940.2	n.*156C>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 21

Bravo AF: 0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TFE3: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.0
DANN	Benign	0.82

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

Other links and lift over

dbSNP: rs2064692276; hg19: chrX-48887870;