ClinVar Genomic variation as it relates to human health
NM_014014.5(SNRNP200):c.3260C>T (p.Ser1087Leu)
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(4); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_014014.5(SNRNP200):c.3260C>T (p.Ser1087Leu)
Variation ID: 7928 Accession: VCV000007928.31
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q11.2 2: 96287968 (GRCh38) [ NCBI UCSC ] 2: 96953706 (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 11, 2015 Apr 15, 2024 Oct 1, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_014014.5:c.3260C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_054733.2:p.Ser1087Leu missense NC_000002.12:g.96287968G>A NC_000002.11:g.96953706G>A NG_016973.1:g.22592C>T O75643:p.Ser1087Leu - Protein change
- S1087L
- Other names
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- Canonical SPDI
- NC_000002.12:96287967:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
The Genome Aggregation Database (gnomAD), exomes 0.00000
Exome Aggregation Consortium (ExAC) 0.00001
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 | ||
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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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SNRNP200 | - | - |
GRCh38 GRCh37 |
1109 | 1230 |
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. |
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Pathogenic (3) |
criteria provided, single submitter
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Apr 8, 2021 | RCV000008390.8 | |
Likely pathogenic (1) |
no assertion criteria provided
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Jan 1, 2015 | RCV000505052.2 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Oct 1, 2023 | RCV001075824.3 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Aug 17, 2023 | RCV001091895.21 |
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. |
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Pathogenic
(Aug 17, 2023)
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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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Invitae
Accession: SCV001399508.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
This missense change has been observed in individuals with autosomal dominant retinitis pigmentosa (PMID: 19878916, 28559085). It has also been observed to segregate with disease … (more)
This missense change has been observed in individuals with autosomal dominant retinitis pigmentosa (PMID: 19878916, 28559085). It has also been observed to segregate with disease in related individuals. This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1087 of the SNRNP200 protein (p.Ser1087Leu). This variant is present in population databases (rs267607077, gnomAD 0.0009%). ClinVar contains an entry for this variant (Variation ID: 7928). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects SNRNP200 function (PMID: 19878916, 24302620). For these reasons, this variant has been classified as Pathogenic. (less)
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Uncertain significance
(Oct 01, 2023)
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criteria provided, single submitter
Method: research
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Retinal dystrophy
Affected status: yes
Allele origin:
germline
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Dept Of Ophthalmology, Nagoya University
Accession: SCV004705429.1
First in ClinVar: Mar 10, 2024 Last updated: Mar 10, 2024 |
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Pathogenic
(Dec 01, 2017)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001248165.20
First in ClinVar: May 12, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 2
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Pathogenic
(Jul 25, 2019)
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criteria provided, single submitter
Method: clinical testing
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Retinal dystrophy
Affected status: yes
Allele origin:
germline
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Blueprint Genetics
Accession: SCV001241460.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
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Pathogenic
(Apr 08, 2021)
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criteria provided, single submitter
Method: research
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Retinitis pigmentosa 33
Affected status: yes
Allele origin:
germline
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Ocular Genomics Institute, Massachusetts Eye and Ear
Accession: SCV001573276.1
First in ClinVar: May 10, 2021 Last updated: May 10, 2021 |
Comment:
The SNRNP200 c.3260C>T variant was identified in an individual with retinitis pigmentosa with a presumed dominant inheritance pattern. Through a review of available evidence we … (more)
The SNRNP200 c.3260C>T variant was identified in an individual with retinitis pigmentosa with a presumed dominant inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PS3, PM1, PM2, PP1, PP3. Based on this evidence we have classified this variant as Pathogenic. (less)
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Pathogenic
(Mar 01, 2014)
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no assertion criteria provided
Method: literature only
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RETINITIS PIGMENTOSA 33
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000028598.3
First in ClinVar: Apr 04, 2013 Last updated: May 16, 2019 |
Comment on evidence:
In 12 affected members of a 4-generation Chinese family with autosomal dominant retinitis pigmentosa mapping to chromosome 2cen-q12.1 (RP33; 610359), previously studied by Zhao et … (more)
In 12 affected members of a 4-generation Chinese family with autosomal dominant retinitis pigmentosa mapping to chromosome 2cen-q12.1 (RP33; 610359), previously studied by Zhao et al. (2006), Zhao et al. (2009) identified a 3260C-T transition in exon 25 of the SNRNP200 gene, resulting in a ser1087-to-leu (S1087L) substitution at a highly conserved residue within the 'ratchet' helix of the first Sec63 domain. The mutation was not found in 13 unaffected family members or in 400 unaffected controls. Assays in budding yeast revealed that a mutation corresponding to S1087L markedly impaired ATP-dependent unwinding of U4/U6 small nuclear RNAs. Cvackova et al. (2014) found that the S1087L substitution had no effect on targeting of BBR2 to nuclear speckles or incorporation of BRR2 into snRNPs. However, the mutation reduced the time with which BRR2 interacted with pre-mRNAs during splicing and increased the use of cryptic splice sites in a reporter based on the beta-globin gene (HBB; 141900). Splicing of other reporter genes was not affected, suggesting gene-specific effects of the mutation on 5-prime splice site selection. (less)
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Likely pathogenic
(Jan 01, 2015)
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no assertion criteria provided
Method: research
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Retinitis pigmentosa
Affected status: yes
Allele origin:
unknown
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NIHR Bioresource Rare Diseases, University of Cambridge
Accession: SCV000598871.1
First in ClinVar: Sep 09, 2017 Last updated: Sep 09, 2017 |
Number of individuals with the variant: 1
Sex: male
Ethnicity/Population group: European
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Retinitis pigmentosa 33
Affected status: yes
Allele origin:
germline
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Genomics England Pilot Project, Genomics England
Accession: SCV001760098.1
First in ClinVar: Jul 27, 2021 Last updated: Jul 27, 2021 |
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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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Clinically Focused Molecular Investigation of 1000 Consecutive Families with Inherited Retinal Disease. | Stone EM | Ophthalmology | 2017 | PMID: 28559085 |
Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease. | Carss KJ | American journal of human genetics | 2017 | PMID: 28041643 |
Retinitis pigmentosa mutations of SNRNP200 enhance cryptic splice-site recognition. | Cvačková Z | Human mutation | 2014 | PMID: 24302620 |
[Targeted sequencing identifies a hotspot mutation SNRNP200 p.S1087L correlates with novel phenotypes in retinitis pigmentosa]. | Chen X | [Zhonghua yan ke za zhi] Chinese journal of ophthalmology | 2013 | PMID: 24499697 |
Autosomal-dominant retinitis pigmentosa caused by a mutation in SNRNP200, a gene required for unwinding of U4/U6 snRNAs. | Zhao C | American journal of human genetics | 2009 | PMID: 19878916 |
A novel locus (RP33) for autosomal dominant retinitis pigmentosa mapping to chromosomal region 2cen-q12.1. | Zhao C | Human genetics | 2006 | PMID: 16612614 |
Text-mined citations for rs267607077 ...
HelpRecord last updated Apr 15, 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.