ClinVar Genomic variation as it relates to human health
NM_139119.3(YY1AP1):c.412-1G>A
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_139119.3(YY1AP1):c.412-1G>A
Variation ID: 523660 Accession: VCV000523660.6
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q22 1: 155672732 (GRCh38) [ NCBI UCSC ] 1: 155642523 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Nov 6, 2018 Aug 24, 2020 Jan 20, 2020 - HGVS
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Nucleotide Protein Molecular
consequenceNM_139119.3:c.412-1G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice acceptor NM_001198899.2:c.379-1G>A splice acceptor NM_001198900.2:c.379-1G>A splice acceptor NM_001198901.2:c.412-1G>A splice acceptor NM_001198902.2:c.412-1G>A splice acceptor NM_001198903.1:c.826-1G>A splice acceptor NM_001198904.1:c.826-1G>A splice acceptor NM_001198905.2:c.412-1G>A splice acceptor NM_001198906.2:c.610-1G>A splice acceptor NM_018253.4:c.379-1G>A splice acceptor NM_139118.3:c.610-1G>A splice acceptor NM_139121.3:c.214-1G>A splice acceptor NC_000001.11:g.155672732C>T NC_000001.10:g.155642523C>T - Protein change
- Other names
- IVS5AS, G-A, -4
- Canonical SPDI
- NC_000001.11:155672731:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- effect on RNA splicing Variation Ontology [VariO:0362]
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Global minor allele
frequency (GMAF) HelpThe 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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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. |
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YY1AP1 | - | - |
GRCh38 GRCh37 |
80 | 140 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jan 20, 2020 | RCV000714980.8 |
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
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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. |
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Pathogenic
(May 02, 2018)
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criteria provided, single submitter
Method: in vitro
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Grange syndrome
(Autosomal recessive inheritance)
Affected status: not applicable
Allele origin:
not applicable
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Institute of Human Genetics Greifswald, Research Division, University Medicine Greifswald
Accession: SCV000747037.1
First in ClinVar: Nov 06, 2018 Last updated: Nov 06, 2018 |
Comment:
The c.826-1G>A variant in YY1AP1 has been identified in a compound heterozygous state with another YY1AP1 splice mutation. Additionally, RT-PCR on RNA from blood lymphocytes … (more)
The c.826-1G>A variant in YY1AP1 has been identified in a compound heterozygous state with another YY1AP1 splice mutation. Additionally, RT-PCR on RNA from blood lymphocytes confirmed skipping of exon 6 which causes a frameshift. In summary, the c.826-1G>A variant meets the ACMG criteria to be classified as pathogenic based upon segregation studies, population frequency data and functional evidence. (less)
Sex: mixed
Tissue: RNA from blood lymphocytes
Comment on evidence:
RT-PCR on RNA from blood lymphocytes confirmed skipping of exon 6 which causes a frameshift.
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Pathogenic
(Jan 20, 2020)
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criteria provided, single submitter
Method: clinical testing
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Grange syndrome
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
maternal
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Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV001430090.1
First in ClinVar: Aug 24, 2020 Last updated: Aug 24, 2020 |
Sex: female
Tissue: blood
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Pathogenic
(Jul 02, 2020)
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no assertion criteria provided
Method: literature only
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GRANGE SYNDROME
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV001370538.1
First in ClinVar: Jul 06, 2020 Last updated: Jul 06, 2020 |
Comment on evidence:
In 3 sibs with Grange syndrome (GRNG; 602531), Rath et al. (2019) identified compound heterozygous mutations in the YY1AP1 gene: IVS5-4G-A (c.826-1G-A), inherited from the … (more)
In 3 sibs with Grange syndrome (GRNG; 602531), Rath et al. (2019) identified compound heterozygous mutations in the YY1AP1 gene: IVS5-4G-A (c.826-1G-A), inherited from the father, and IVS6+23T-G (c.977+23T-G, 607860.0007), inherited from the mother. The mutations were identified by sequencing of near-splice regions and Sanger sequencing, following failure of whole-exome sequencing to identify a candidate gene. A younger sib, aged 12 years, was heterozygous for the maternal mutation. The mutation in intron 5 was predicted to cause skipping of exon 6. The mutation in intron 6 was predicted to create a novel donor splice site in intron 6, resulting in a frameshift due to exonization of 22 intronic nucleotides (Ala333GlyfsTer10). The variants were classified as loss-of-function mutations and as pathogenic according to ACMG guidelines. The splice site defects were confirmed by RT-PCR in all 4 sibs and the carrier parents. The parents were asymptomatic and had no stenoocclusive lesions, and the 12-year-old sib had as yet no vascular lesions. The c.977+23T-G variant was not present in the gnomAD database, whereas the c.826-1G-A variant was present in 3 heterozygotes. Functional studies were not performed. (less)
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Germline Functional Evidence
Functional
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The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
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A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
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A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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effect on RNA splicing
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Institute of Human Genetics Greifswald, Research Division, University Medicine Greifswald
Accession: SCV000747037.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Identification of pathogenic YY1AP1 splice variants in siblings with Grange syndrome by whole exome sequencing. | Rath M | American journal of medical genetics. Part A | 2019 | PMID: 30556293 |
Text-mined citations for rs199653824 ...
HelpRecord last updated Apr 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.