VCV000009779.2 - ClinVar

NC_000023.11:g.73852757G>C

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.

Pathogenic

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.73852757G>C

Variation ID: 9779 Accession: VCV000009779.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xq13.2 X: 73852757 (GRCh38) [ NCBI UCSC ] X: 73072592 (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	Oct 2, 2016	Oct 7, 2023	Nov 1, 1997

HGVS

Nucleotide	Protein	Molecular consequence
NC_000023.11:g.73852757G>C
NC_000023.10:g.73072592G>C
NG_016172.1:g.4997C>G

Protein change

Other names

C-G, -43

Canonical SPDI

NC_000023.11:73852756:G:C

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.

0.00053 (C)

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

1000 Genomes Project 0.00053

1000 Genomes Project 30x 0.00062

Links

OMIM: 314670.0001 dbSNP: rs773396320 VarSome

Comment on variant

NCBI staff provided an HGVS expression for this allele from the sequence in Figure 2 of the paper by Plenge et al., 1997 (PubMed 9354806).

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.
XIST		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	27	169

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.
X inactivation, familial skewed, 1	Pathogenic (1)	no assertion criteria provided	Nov 1, 1997	RCV000010433.5

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.
Pathogenic (Nov 01, 1997)	no assertion criteria provided Method: literature only	X INACTIVATION, FAMILIAL SKEWED, 1 Affected status: not provided Allele origin: germline	OMIM Accession: SCV000030659.3 First in ClinVar: Apr 04, 2013 Last updated: Oct 07, 2023	Publications: PubMed (2) PubMed: 9354806‚ 8825575 Comment on evidence: Plenge et al. (1997) identified a mutation in the XIST minimal promoter in multiple females in a family reported by Rupert et al. (1995) as … (more) Plenge et al. (1997) identified a mutation in the XIST minimal promoter in multiple females in a family reported by Rupert et al. (1995) as showing nonrandom X chromosome inactivation (300087). The mutation was a C-to-G transversion at position -43 in the minimal promoter on the preferentially inactive X chromosome. The -43 mutation created a novel HhaI restriction site that was used to test for the presence of the mutation in a large series of unrelated females, representing 1,166 independent X chromosomes. The mutation was found on only 1 additional chromosome in this dataset, ruling out that the mutation represented a common polymorphism. The heterozygous female identified by this screen was from a large family with Snyder-Robinson mental retardation syndrome (309583), which maps to Xp22.12-p21.3. Haplotype analysis indicated that the 2 families were not related. Subsequent analysis in the second family revealed 6 additional females and 4 males who had inherited the XIST mutation. (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
A promoter mutation in the XIST gene in two unrelated families with skewed X-chromosome inactivation.	Plenge RM	Nature genetics	1997	PMID: 9354806
Direct detection of non-random X chromosome inactivation by use of a transcribed polymorphism in the XIST gene.	Rupert JL	European journal of human genetics : EJHG	1995	PMID: 8825575

Text-mined citations for rs773396320 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 01, 2024

ClinVar Genomic variation as it relates to human health

NC_000023.11:g.73852757G>C

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs773396320 ...