ClinVar Genomic variation as it relates to human health
NM_020191.4(MRPS22):c.605G>A (p.Arg202His)
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.
Pathogenic(1); Uncertain significance(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_020191.4(MRPS22):c.605G>A (p.Arg202His)
Variation ID: 441255 Accession: VCV000441255.4
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3q23 3: 139350279 (GRCh38) [ NCBI UCSC ] 3: 139069121 (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 Mar 26, 2018 Jan 26, 2024 Jan 10, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_020191.4:c.605G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_064576.1:p.Arg202His missense NM_001363857.1:c.482G>A NP_001350786.1:p.Arg161His missense NM_001363893.1:c.602G>A NP_001350822.1:p.Arg201His missense NC_000003.12:g.139350279G>A NC_000003.11:g.139069121G>A NG_012174.1:g.11261G>A - Protein change
- R202H, R201H, R161H
- Other names
- MRPS22, ARG202HIS (rs753345594)
- Canonical SPDI
- NC_000003.12:139350278:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- variation affecting protein Variation Ontology [VariO:0002]
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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) 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD) 0.00002
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
Help
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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MRPS22 | - | - |
GRCh38 GRCh37 |
164 | 210 |
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
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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 (1) |
criteria provided, single submitter
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Oct 16, 2017 | RCV000590993.2 | |
Pathogenic (1) |
no assertion criteria provided
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Sep 12, 2018 | RCV000680194.1 | |
Uncertain significance (1) |
criteria provided, single submitter
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Oct 14, 2021 | RCV001857298.2 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 10, 2024 | RCV003483645.2 |
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
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. |
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Pathogenic
(Oct 16, 2017)
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criteria provided, single submitter
Method: research
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46 XX gonadal dysgenesis
(Autosomal recessive inheritance)
Affected status: yes, no
Allele origin:
germline
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David Buchner Laboratory, Case Western Reserve University
Accession: SCV000607729.1
First in ClinVar: Mar 26, 2018 Last updated: Mar 26, 2018 |
Comment:
Four individuals from two independent consanguineous families with 46,XX gonadal dysgenesis were found to be homozygous for nonsynonymous variants in MRPS22. The unaffected parents and … (more)
Four individuals from two independent consanguineous families with 46,XX gonadal dysgenesis were found to be homozygous for nonsynonymous variants in MRPS22. The unaffected parents and siblings were not homozygous for these mutations. In one of the consanguineous families, the region containing MRPS22 was the only region of homozygosity that segregated with the disease and the variant in MRPS22 was the only nonsynonymous variant in this interval. Additional support for the clinical significance comes from studies in Drosophila that demonstrate mRpS22 is required for fertility and germ cell development. (less)
Observation 1:
Sex: female
Ethnicity/Population group: Israeli-Christian Arab
Geographic origin: Israel
Observation 2:
Sex: male
Ethnicity/Population group: Israeli-Christian Arab
Geographic origin: Israel
Observation 3:
Sex: female
Ethnicity/Population group: Israeli-Christian Arab
Geographic origin: Israel
Observation 4:
Sex: male
Ethnicity/Population group: Israeli-Christian Arab
Geographic origin: Israel
Observation 5:
Sex: female
Ethnicity/Population group: Israeli-Christian Arab
Geographic origin: Israel
Method: Whole exome sequencing confirmed by Sanger Sequencing
Observation 6:
Sex: male
Ethnicity/Population group: Israeli-Christian Arab
Geographic origin: Israel
Observation 7:
Clinical Features:
46,XX gonadal dysgenesis (present)
Age: 10-19 years
Sex: female
Ethnicity/Population group: Israeli-Christian Arab
Geographic origin: Israel
Method: Whole exome sequencing confirmed by Sanger Sequencing
Observation 8:
Clinical Features:
46,XX gonadal dysgenesis (present)
Age: 10-19 years
Sex: female
Ethnicity/Population group: Israeli-Christian Arab
Geographic origin: Israel
Observation 9:
Clinical Features:
46,XX gonadal dysgenesis (present)
Age: 10-19 years
Sex: female
Ethnicity/Population group: Israeli-Christian Arab
Geographic origin: Israel
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Uncertain significance
(Oct 14, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002202848.1
First in ClinVar: Mar 28, 2022 Last updated: Mar 28, 2022 |
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Uncertain significance
(Jan 10, 2024)
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criteria provided, single submitter
Method: clinical testing
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Muscular dystrophy, adult-onset, with leukoencephalopathy
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV004228501.1
First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024 |
Clinical Features:
Leukoencephalopathy (present) , Leukodystrophy (present) , Sensorimotor neuropathy (present) , Foot dorsiflexor weakness (present)
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Pathogenic
(Sep 12, 2018)
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no assertion criteria provided
Method: literature only
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OVARIAN DYSGENESIS 7
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000807658.1
First in ClinVar: Sep 16, 2018 Last updated: Sep 16, 2018 |
Comment on evidence:
In 2 46,XX sisters and their 46,XX cousin from a large consanguineous Israeli-Christian Arab family with delayed puberty, elevated gonadotropins, and ovarian dysgenesis (ODG7; 618117), … (more)
In 2 46,XX sisters and their 46,XX cousin from a large consanguineous Israeli-Christian Arab family with delayed puberty, elevated gonadotropins, and ovarian dysgenesis (ODG7; 618117), Chen et al. (2018) identified homozygosity for a c.605G-A transition (c.605G-A, NM_020191; SCV000607729) in the MRPS22 gene, resulting in an arg202-to-his (R202H) substitution at a highly conserved residue within an internal region of the protein, between an alpha-helical subdomain and a beta-sheet+1 alpha helix subdomain. The mutation segregated fully with disease in the family and was present in the gnomAD database at an allele frequency of 0.00001218 (no homozygotes). Functional analysis in patient primary fibroblasts showed no detectable effect of the R202H mutant on MRPS22 mRNA or protein expression levels, on mitochondrial rRNA expression levels, or on mitochondrial function, compared to controls. (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
Help
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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variation affecting protein
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David Buchner Laboratory, Case Western Reserve University
Accession: SCV000607729.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Mutations in the mitochondrial ribosomal protein MRPS22 lead to primary ovarian insufficiency. | Chen A | Human molecular genetics | 2018 | PMID: 29566152 |
Text-mined citations for rs753345594 ...
HelpRecord last updated Sep 29, 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.