VCV000992855.2 - ClinVar

NM_006521.6(TFE3):c.557C>T (p.Pro186Leu)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(2)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Likely pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_006521.6(TFE3):c.557C>T (p.Pro186Leu)

Variation ID: 992855 Accession: VCV000992855.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xp11.23 X: 49038420 (GRCh38) [ NCBI UCSC ] X: 48895945 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jan 17, 2021	Oct 30, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NM_006521.6:c.557C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_006512.2:p.Pro186Leu	missense
NM_001282142.2:c.242C>T	NP_001269071.1:p.Pro81Leu	missense
NC_000023.11:g.49038420G>A
NC_000023.10:g.48895945G>A
NG_016297.2:g.10041C>T

... more HGVS ... less HGVS

Protein change

P186L, P81L

Other names

Canonical SPDI

NC_000023.11:49038419:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

OMIM: 314310.0004 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
TFE3		-	-	GRCh38 GRCh38 GRCh37	94	259

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not provided	Likely pathogenic (1)	criteria provided, single submitter	-	RCV001281623.2
Intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies	Pathogenic (1)	no assertion criteria provided	Oct 27, 2021	RCV001732109.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely pathogenic (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Not provided Affected status: yes Allele origin: germline	Laboratoire de Génétique Moléculaire, CHU Bordeaux Accession: SCV001468953.1 First in ClinVar: Jan 17, 2021 Last updated: Jan 17, 2021
Pathogenic (Oct 27, 2021)	no assertion criteria provided Method: literature only	INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, WITH PIGMENTARY MOSAICISM AND COARSE FACIES Affected status: not provided Allele origin: germline	OMIM Accession: SCV001984763.1 First in ClinVar: Oct 30, 2021 Last updated: Oct 30, 2021	Publications: PubMed (1) PubMed: 30595499 Comment on evidence: In an 18-year-old woman (patient 5) with X-linked syndromic intellectual developmental disorder with pigmentary mosaicism and coarse facies (MRXSPF; 301066), Villegas et al. (2019) identified … (more) In an 18-year-old woman (patient 5) with X-linked syndromic intellectual developmental disorder with pigmentary mosaicism and coarse facies (MRXSPF; 301066), Villegas et al. (2019) identified de novo heterozygosity for a c.557C-T transversion (c.557C-T, NM_006521.4) in exon 4 of the TFE3 gene, resulting in a pro186-to-leu (P186L) substitution at a conserved residue. The mutation was identified by whole-exome sequencing. The mutation was not present in the ExAC database. The mutation is predicted to affect an amino acid that may be important for interaction with the Rag heterodimer. (less)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Lysosomal Signaling Licenses Embryonic Stem Cell Differentiation via Inactivation of Tfe3.	Villegas F	Cell stem cell	2019	PMID: 30595499

Text-mined citations for this variant ...

Record last updated Jun 23, 2024

ClinVar Genomic variation as it relates to human health

NM_006521.6(TFE3):c.557C>T (p.Pro186Leu)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...