ClinVar Genomic variation as it relates to human health
NM_012280.4(FTSJ1):c.655G>A (p.Asp219Asn)
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_012280.4(FTSJ1):c.655G>A (p.Asp219Asn)
Variation ID: 10894 Accession: VCV000010894.8
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xp11.23 X: 48481715 (GRCh38) [ NCBI UCSC ] X: 48340103 (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 Apr 4, 2013 Nov 11, 2023 May 4, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_012280.4:c.655G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_036412.1:p.Asp219Asn missense NM_001282157.1:c.244G>A NP_001269086.1:p.Asp82Asn missense NM_012280.2:c.655G>A NM_012280.3:c.655G>A NM_177434.1:c.655G>A NP_803183.1:p.Asp219Asn missense NM_177439.3:c.655G>A NP_803188.1:p.Asp219Asn missense NC_000023.11:g.48481715G>A NC_000023.10:g.48340103G>A NG_008879.1:g.10555G>A - Protein change
- D219N, D82N
- Other names
- EX9DEL
- Canonical SPDI
- NC_000023.11:48481714:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- exon loss Variation Ontology [VariO:0381]
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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.
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- Links
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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FTSJ1 | Some evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
73 | 236 |
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 (2) |
criteria provided, single submitter
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May 4, 2023 | RCV000011641.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 2, 2023 | RCV003114186.3 |
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
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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
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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
(Feb 02, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV003798915.2
First in ClinVar: Feb 13, 2023 Last updated: Nov 11, 2023 |
Comment:
Published cDNA studies show a deletion of exon 9, which is predicted to be in-frame (Freude et al. 2004); Not observed at significant frequency in … (more)
Published cDNA studies show a deletion of exon 9, which is predicted to be in-frame (Freude et al. 2004); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 10398246, 17221867, 15162322) (less)
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Pathogenic
(May 04, 2023)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, X-linked 9
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003933895.1
First in ClinVar: Jun 24, 2023 Last updated: Jun 24, 2023 |
Comment:
Variant summary: FTSJ1 c.655G>A (p.Asp219Asn) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign … (more)
Variant summary: FTSJ1 c.655G>A (p.Asp219Asn) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. In addition, this variant is located to the last nucleotide of exon 9, and therefore can affect splicing. Several computational tools predict a significant impact on normal splicing: three predict the variant weakens a 5' donor site, one predicts the variant abolishes a 5' splicing donor site. At least one publication reported experimental evidence confirming that this variant affects mRNA splicing, finding that the variant resulted in skipping of exon 9, with an in-frame deletion at the protein level (Freude_2004) that is predicted to disrupt the C-terminal part of the S-AdoMet-binding domain (Freude_2004). The variant was absent in 180681 control chromosomes. c.655G>A has been reported in the literature in several related individuals with Intellectual disability, X-linked 9, and the variant was shown to segregate with disease in these related individuals (e.g., Freude_2004, deBrouwer_2007). These data indicate that the variant is likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 15162322, 17221867). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Aug 01, 2004)
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no assertion criteria provided
Method: literature only
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INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 9
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000031873.2
First in ClinVar: Apr 04, 2013 Last updated: Aug 24, 2021 |
Comment on evidence:
In the family reported by Hamel et al. (1999) and designated MRX44 (XLID9; 309549), affected males had mild to moderate mental retardation. Freude et al. … (more)
In the family reported by Hamel et al. (1999) and designated MRX44 (XLID9; 309549), affected males had mild to moderate mental retardation. Freude et al. (2004) found a single-nucleotide substitution (655G-A) at the last nucleotide of exon 9 in this family. Subsequent amplification of patient cDNA resulted in a fragment that was smaller than expected; direct sequencing of this specific product showed that exon 9 was absent. The absence introduced no frameshift in the FTSJ1 open reading frame, but the resulting FTSJ1 protein lacked 28 amino acids, which altered its structure and probably also its function. (less)
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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
HelpTitle | Author | Journal | Year | Link |
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Mutation frequencies of X-linked mental retardation genes in families from the EuroMRX consortium. | de Brouwer AP | Human mutation | 2007 | PMID: 17221867 |
Mutations in the FTSJ1 gene coding for a novel S-adenosylmethionine-binding protein cause nonsyndromic X-linked mental retardation. | Freude K | American journal of human genetics | 2004 | PMID: 15162322 |
Four families (MRX43, MRX44, MRX45, MRX52) with nonspecific X-linked mental retardation: clinical and psychometric data and results of linkage analysis. | Hamel BC | American journal of medical genetics | 1999 | PMID: 10398246 |
Text-mined citations for this variant ...
HelpRecord last updated Nov 11, 2023
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.