VCV000031938.1 - ClinVar

NC_000023.11:g.(155524633_155545096)_(155545276_155612791)del

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.

(1)

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.

risk factor

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000023.11:g.(155524633_155545096)_(155545276_155612791)del

Variation ID: 31938 Accession: VCV000031938.1

Type and length

Deletion, 181 bp

Location

Cytogenetic: Xq28 X: 155524633-155612791 (GRCh38) [ 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	Apr 20, 2016	Apr 20, 2016	Oct 23, 2012

HGVS

Nucleotide	Protein	Molecular consequence
NC_000023.11:g.(155524633_155545096)_(155545276_155612791)del

Protein change

Other names

EX2DEL

Canonical SPDI

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

dbVar: nssv7487218 dbVar: nsv1197531 OMIM: 300777.0001 VarSome

Comment on variant

Genomic deletions of 5.7 to 15.9-kb spanning exon 2 plus flanking intronic sequences from gene TMLHE.

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.
TMLHE		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	64	288
SPRY3		-	-	GRCh38 GRCh38	2	132

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.
Epsilon-trimethyllysine hydroxylase deficiency	risk factor (1)	no assertion criteria provided	Oct 23, 2012	RCV000024616.4

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.
risk factor (Oct 23, 2012)	no assertion criteria provided Method: literature only	AUTISM, SUSCEPTIBILITY TO, X-LINKED 6 Affected status: not provided Allele origin: germline	OMIM Accession: SCV000050482.3 First in ClinVar: Apr 04, 2013 Last updated: Apr 20, 2016	Publications: PubMed (3) PubMed: 21865298‚ 22566635‚ 23092983 Comment on evidence: In a male patient with X-linked autism-6 (AUTSX6; 300872), Celestino-Soper et al. (2011) identified a deletion of exon 2 of the TMLHE gene. In a … (more) In a male patient with X-linked autism-6 (AUTSX6; 300872), Celestino-Soper et al. (2011) identified a deletion of exon 2 of the TMLHE gene. In a further report, Celestino-Soper et al. (2012) stated that they had identified a total of 16 male autism probands, 6 affected male sibs of probands, and 24 healthy adult males with deletions of exon 2, indicating that this is a relatively common copy number variant. For 28 of 29 well-characterized deletions, size ranged from 5.7 kb (chrX:154772351-154778095, GRCh37) to 15.9 kb (chrX:154762300-154778227, GRCh37) and only exon 2 was deleted; one additional deletion of 59.6 kb (chrX:154734433-154794037, GRCh37) removed exons 2 through 6. Based on position, size, and sequence, there were at least 14 different deletion junctions among 29 unrelated families. Sequencing of the breakpoints of many deletions showed that almost all junctions occurred in long interspersed elements and short interspersed elements in the introns flanking exon 2. Nava et al. (2012) identified the exon 2 TMLHE deletion in 1 of 896 male controls and in 3 of 691 male patients with autism spectrum disorder (p = 0.3). One of the 3 patients with the deletion had an affected brother who did not carry the deletion. The findings were consistent with the variant being a susceptibility factor for autism, and suggested that it may not be as rare as previously thought. (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
Analysis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes, including TMLHE.	Nava C	Translational psychiatry	2012	PMID: 23092983
A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism.	Celestino-Soper PB	Proceedings of the National Academy of Sciences of the United States of America	2012	PMID: 22566635
Use of array CGH to detect exonic copy number variants throughout the genome in autism families detects a novel deletion in TMLHE.	Celestino-Soper PB	Human molecular genetics	2011	PMID: 21865298

Text-mined citations for this variant ...

Record last updated Mar 26, 2023

ClinVar Genomic variation as it relates to human health

NC_000023.11:g.(155524633_155545096)_(155545276_155612791)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...