This variant was classified as: Uncertain significance. The available evidence favors the pathogenic nature of this variant, however the currently available data is insufficient to conclusively support its pathogenic nature. Thus this variant is classified as Uncertain significance - favor pathogenic. The following ACMG criteria were applied in classifying this variant: PP3.
ClinVar Genomic variation as it relates to human health
NM_014989.7(RIMS1):c.2896C>T (p.Arg966Cys)
Germline
Classification
Help
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.
(2)
Help
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.
Uncertain significance
2
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_014989.7(RIMS1):c.2896C>T (p.Arg966Cys)
Variation ID: 930473 Accession: VCV000930473.6
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 6q13 6: 72967953 (GRCh37) [ NCBI UCSC ] 6: 72258250 (GRCh38) [ 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 Jul 4, 2020 Feb 28, 2024 Jan 4, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_014989.7:c.2896C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_055804.2:p.Arg966Cys missense NM_001168407.2:c.1315C>T NP_001161879.1:p.Arg439Cys missense NM_001168408.2:c.1318C>T NP_001161880.1:p.Arg440Cys missense NM_001168409.2:c.1075C>T NP_001161881.1:p.Arg359Cys missense NM_001168410.2:c.1273C>T NP_001161882.1:p.Arg425Cys missense NM_001350414.2:c.1318C>T NP_001337343.1:p.Arg440Cys missense NM_001350415.2:c.1315C>T NP_001337344.1:p.Arg439Cys missense NM_001350416.2:c.1318C>T NP_001337345.1:p.Arg440Cys missense NM_001350417.2:c.1318C>T NP_001337346.1:p.Arg440Cys missense NM_001350418.2:c.1315C>T NP_001337347.1:p.Arg439Cys missense NM_001350419.2:c.1315C>T NP_001337348.1:p.Arg439Cys missense NM_001350420.2:c.1318C>T NP_001337349.1:p.Arg440Cys missense NM_001350421.2:c.1246C>T NP_001337350.1:p.Arg416Cys missense NM_001350422.2:c.1315C>T NP_001337351.1:p.Arg439Cys missense NM_001350423.2:c.1315C>T NP_001337352.1:p.Arg439Cys missense NM_001350424.2:c.1249C>T NP_001337353.1:p.Arg417Cys missense NM_001350425.2:c.1315C>T NP_001337354.1:p.Arg439Cys missense NM_001350426.2:c.1318C>T NP_001337355.1:p.Arg440Cys missense NM_001350427.2:c.1315C>T NP_001337356.1:p.Arg439Cys missense NM_001350428.2:c.1249C>T NP_001337357.1:p.Arg417Cys missense NM_001350429.2:c.1318C>T NP_001337358.1:p.Arg440Cys missense NM_001350430.2:c.1246C>T NP_001337359.1:p.Arg416Cys missense NM_001350431.2:c.1318C>T NP_001337360.1:p.Arg440Cys missense NM_001350432.2:c.1315C>T NP_001337361.1:p.Arg439Cys missense NM_001350433.2:c.1318C>T NP_001337362.1:p.Arg440Cys missense NM_001350434.2:c.1315C>T NP_001337363.1:p.Arg439Cys missense NM_001350435.2:c.1315C>T NP_001337364.1:p.Arg439Cys missense NM_001350436.2:c.1315C>T NP_001337365.1:p.Arg439Cys missense NM_001350437.2:c.1246C>T NP_001337366.1:p.Arg416Cys missense NM_001350438.2:c.1315C>T NP_001337367.1:p.Arg439Cys missense NM_001350439.2:c.1318C>T NP_001337368.1:p.Arg440Cys missense NM_001350440.2:c.1315C>T NP_001337369.1:p.Arg439Cys missense NM_001350441.2:c.1315C>T NP_001337370.1:p.Arg439Cys missense NM_001350442.2:c.1318C>T NP_001337371.1:p.Arg440Cys missense NM_001350443.2:c.1315C>T NP_001337372.1:p.Arg439Cys missense NM_001350444.2:c.1315C>T NP_001337373.1:p.Arg439Cys missense NM_001350445.2:c.1315C>T NP_001337374.1:p.Arg439Cys missense NM_001350446.2:c.1318C>T NP_001337375.1:p.Arg440Cys missense NM_001350447.2:c.1315C>T NP_001337376.1:p.Arg439Cys missense NM_001350448.2:c.1318C>T NP_001337377.1:p.Arg440Cys missense NM_001350449.2:c.1315C>T NP_001337378.1:p.Arg439Cys missense NM_001350450.2:c.1246C>T NP_001337379.1:p.Arg416Cys missense NM_001350452.2:c.1318C>T NP_001337381.1:p.Arg440Cys missense NM_001350454.2:c.1315C>T NP_001337383.1:p.Arg439Cys missense NM_001350455.2:c.1318C>T NP_001337384.1:p.Arg440Cys missense NM_001350456.2:c.1315C>T NP_001337385.1:p.Arg439Cys missense NM_001350457.2:c.1318C>T NP_001337386.1:p.Arg440Cys missense NM_001350458.2:c.1318C>T NP_001337387.1:p.Arg440Cys missense NM_001350459.2:c.1249C>T NP_001337388.1:p.Arg417Cys missense NM_001350460.2:c.1318C>T NP_001337389.1:p.Arg440Cys missense NM_001350461.2:c.1072C>T NP_001337390.1:p.Arg358Cys missense NM_001350462.2:c.1249C>T NP_001337391.1:p.Arg417Cys missense NM_001350463.2:c.1072C>T NP_001337392.1:p.Arg358Cys missense NM_001350464.2:c.1075C>T NP_001337393.1:p.Arg359Cys missense NM_001350465.2:c.1075C>T NP_001337394.1:p.Arg359Cys missense NM_001350466.2:c.1075C>T NP_001337395.1:p.Arg359Cys missense NM_001350467.2:c.1075C>T NP_001337396.1:p.Arg359Cys missense NM_001350468.2:c.1072C>T NP_001337397.1:p.Arg358Cys missense NM_001350469.2:c.1075C>T NP_001337398.1:p.Arg359Cys missense NM_001350470.2:c.1273C>T NP_001337399.1:p.Arg425Cys missense NM_001350471.2:c.1246C>T NP_001337400.1:p.Arg416Cys missense NM_001350472.2:c.1270C>T NP_001337401.1:p.Arg424Cys missense NM_001350473.2:c.1273C>T NP_001337402.1:p.Arg425Cys missense NM_001350474.2:c.1273C>T NP_001337403.1:p.Arg425Cys missense NC_000006.12:g.72258250C>T NC_000006.11:g.72967953C>T NG_016209.1:g.376304C>T - Protein change
- R416C, R424C, R358C, R417C, R425C, R966C, R359C, R439C, R440C
- Other names
- -
- Canonical SPDI
- NC_000006.12:72258249:C:T
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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
Help
The frequency of the allele represented by this VCV record.
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Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| RIMS1 | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1141 | 1188 | |
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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Apr 9, 2019 | RCV001196149.2 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Jan 4, 2024 | RCV002560216.3 |
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
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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|---|---|---|---|---|---|
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Uncertain significance
(Apr 09, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Cone-rod dystrophy 7
Affected status: yes
Allele origin:
unknown
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001366670.2
First in ClinVar: Jul 04, 2020 Last updated: Jul 04, 2020 |
Comment:
This variant was classified as: Uncertain significance. The available evidence favors the pathogenic nature of this variant, however the currently available data is insufficient to … (more)
This variant was classified as: Uncertain significance. The available evidence favors the pathogenic nature of this variant, however the currently available data is insufficient to conclusively support its pathogenic nature. Thus this variant is classified as Uncertain significance - favor pathogenic. The following ACMG criteria were applied in classifying this variant: PP3. (less)
|
|
|
Uncertain significance
(Jan 04, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002955600.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 28, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 966 of the RIMS1 protein … (more)
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 966 of the RIMS1 protein (p.Arg966Cys). This variant is present in population databases (rs764444309, gnomAD 0.006%). This missense change has been observed in individual(s) with autism spectrum disorder (PMID: 28191889). ClinVar contains an entry for this variant (Variation ID: 930473). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
|
Comment:
Comment:
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 966 of the RIMS1 protein (p.Arg966Cys). This variant is present in population databases (rs764444309, gnomAD 0.006%). This missense change has been observed in individual(s) with autism spectrum disorder (PMID: 28191889). ClinVar contains an entry for this variant (Variation ID: 930473). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
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. |
Comment:
This variant was classified as: Uncertain significance. The available evidence favors the pathogenic nature of this variant, however the currently available data is insufficient to conclusively support its pathogenic nature. Thus this variant is classified as Uncertain significance - favor pathogenic. The following ACMG criteria were applied in classifying this variant: PP3.
Comment:
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 966 of the RIMS1 protein (p.Arg966Cys). This variant is present in population databases (rs764444309, gnomAD 0.006%). This missense change has been observed in individual(s) with autism spectrum disorder (PMID: 28191889). ClinVar contains an entry for this variant (Variation ID: 930473). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. | Stessman HA | Nature genetics | 2017 | PMID: 28191889 |
Text-mined citations for rs764444309 ...
HelpThese 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 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.