This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1685 of the RIMS1 protein (p.Thr1685Ala). This variant is present in population databases (rs200035429, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RIMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 835781). 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 tolerated. 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.
ClinVar Genomic variation as it relates to human health
NM_014989.7(RIMS1):c.5053A>G (p.Thr1685Ala)
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, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_014989.7(RIMS1):c.5053A>G (p.Thr1685Ala)
Variation ID: 835781 Accession: VCV000835781.6
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 6q13 6: 72400688 (GRCh38) [ NCBI UCSC ] 6: 73110390 (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 15, 2020 Feb 14, 2024 Jan 4, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_014989.7:c.5053A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_055804.2:p.Thr1685Ala missense NM_001168407.2:c.3013A>G NP_001161879.1:p.Thr1005Ala missense NM_001168408.2:c.2428A>G NP_001161880.1:p.Thr810Ala missense NM_001168409.2:c.2257A>G NP_001161881.1:p.Thr753Ala missense NM_001168410.2:c.2455A>G NP_001161882.1:p.Thr819Ala missense NM_001168411.2:c.634A>G NP_001161883.1:p.Thr212Ala missense NM_001350414.2:c.2974A>G NP_001337343.1:p.Thr992Ala missense NM_001350415.2:c.3070A>G NP_001337344.1:p.Thr1024Ala missense NM_001350416.2:c.3019A>G NP_001337345.1:p.Thr1007Ala missense NM_001350417.2:c.2500A>G NP_001337346.1:p.Thr834Ala missense NM_001350418.2:c.2992A>G NP_001337347.1:p.Thr998Ala missense NM_001350419.2:c.2272A>G NP_001337348.1:p.Thr758Ala missense NM_001350420.2:c.3127A>G NP_001337349.1:p.Thr1043Ala missense NM_001350421.2:c.2872A>G NP_001337350.1:p.Thr958Ala missense NM_001350422.2:c.2497A>G NP_001337351.1:p.Thr833Ala missense NM_001350423.2:c.2761A>G NP_001337352.1:p.Thr921Ala missense NM_001350424.2:c.2359A>G NP_001337353.1:p.Thr787Ala missense NM_001350425.2:c.2971A>G NP_001337354.1:p.Thr991Ala missense NM_001350426.2:c.2347A>G NP_001337355.1:p.Thr783Ala missense NM_001350427.2:c.2425A>G NP_001337356.1:p.Thr809Ala missense NM_001350428.2:c.2431A>G NP_001337357.1:p.Thr811Ala missense NM_001350429.2:c.2791A>G NP_001337358.1:p.Thr931Ala missense NM_001350430.2:c.2428A>G NP_001337359.1:p.Thr810Ala missense NM_001350431.2:c.3109A>G NP_001337360.1:p.Thr1037Ala missense NM_001350432.2:c.2335A>G NP_001337361.1:p.Thr779Ala missense NM_001350433.2:c.3100A>G NP_001337362.1:p.Thr1034Ala missense NM_001350434.2:c.2575A>G NP_001337363.1:p.Thr859Ala missense NM_001350435.2:c.2962A>G NP_001337364.1:p.Thr988Ala missense NM_001350436.2:c.3205A>G NP_001337365.1:p.Thr1069Ala missense NM_001350437.2:c.2956A>G NP_001337366.1:p.Thr986Ala missense NM_001350438.2:c.2680A>G NP_001337367.1:p.Thr894Ala missense NM_001350439.2:c.2944A>G NP_001337368.1:p.Thr982Ala missense NM_001350440.2:c.2344A>G NP_001337369.1:p.Thr782Ala missense NM_001350441.2:c.2941A>G NP_001337370.1:p.Thr981Ala missense NM_001350442.2:c.2683A>G NP_001337371.1:p.Thr895Ala missense NM_001350443.2:c.2914A>G NP_001337372.1:p.Thr972Ala missense NM_001350444.2:c.2788A>G NP_001337373.1:p.Thr930Ala missense NM_001350445.2:c.2581A>G NP_001337374.1:p.Thr861Ala missense NM_001350446.2:c.3199A>G NP_001337375.1:p.Thr1067Ala missense NM_001350447.2:c.2860A>G NP_001337376.1:p.Thr954Ala missense NM_001350448.2:c.3016A>G NP_001337377.1:p.Thr1006Ala missense NM_001350449.2:c.2407A>G NP_001337378.1:p.Thr803Ala missense NM_001350450.2:c.2356A>G NP_001337379.1:p.Thr786Ala missense NM_001350454.2:c.2923A>G NP_001337383.1:p.Thr975Ala missense NM_001350455.2:c.2275A>G NP_001337384.1:p.Thr759Ala missense NM_001350456.2:c.3196A>G NP_001337385.1:p.Thr1066Ala missense NM_001350457.2:c.2953A>G NP_001337386.1:p.Thr985Ala missense NM_001350458.2:c.3022A>G NP_001337387.1:p.Thr1008Ala missense NM_001350459.2:c.2875A>G NP_001337388.1:p.Thr959Ala missense NM_001350460.2:c.2893A>G NP_001337389.1:p.Thr965Ala missense NM_001350461.2:c.2743A>G NP_001337390.1:p.Thr915Ala missense NM_001350462.2:c.3058A>G NP_001337391.1:p.Thr1020Ala missense NM_001350463.2:c.2698A>G NP_001337392.1:p.Thr900Ala missense NM_001350464.2:c.2701A>G NP_001337393.1:p.Thr901Ala missense NM_001350465.2:c.2185A>G NP_001337394.1:p.Thr729Ala missense NM_001350466.2:c.2704A>G NP_001337395.1:p.Thr902Ala missense NM_001350467.2:c.2620A>G NP_001337396.1:p.Thr874Ala missense NM_001350468.2:c.2545A>G NP_001337397.1:p.Thr849Ala missense NM_001350469.2:c.2773A>G NP_001337398.1:p.Thr925Ala missense NM_001350470.2:c.2461A>G NP_001337399.1:p.Thr821Ala missense NM_001350471.2:c.2854A>G NP_001337400.1:p.Thr952Ala missense NM_001350472.2:c.2380A>G NP_001337401.1:p.Thr794Ala missense NM_001350473.2:c.2383A>G NP_001337402.1:p.Thr795Ala missense NM_001350474.2:c.2746A>G NP_001337403.1:p.Thr916Ala missense NC_000006.12:g.72400688A>G NC_000006.11:g.73110390A>G NG_016209.1:g.518741A>G - Protein change
- T1007A, T729A, T753A, T819A, T833A, T834A, T861A, T915A, T916A, T972A, T985A, T1008A, T1034A, T1037A, T1685A, T758A, T759A, T786A, T787A, T794A, T849A, T859A, T874A, T895A, T925A, T954A, T958A, T981A, T991A, T1005A, T1020A, T1067A, T1069A, T212A, T779A, T783A, T821A, T900A, T901A, T902A, T921A, T959A, T965A, T988A, T1006A, T1024A, T1043A, T1066A, T782A, T795A, T803A, T809A, T810A, T811A, T894A, T930A, T931A, T952A, T975A, T982A, T986A, T992A, T998A
- Other names
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- Canonical SPDI
- NC_000006.12:72400687:A:G
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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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The Genome Aggregation Database (gnomAD) 0.00013
Exome Aggregation Consortium (ExAC) 0.00015
The Genome Aggregation Database (gnomAD), exomes 0.00015
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00017
Trans-Omics for Precision Medicine (TOPMed) 0.00015
- 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 (2) |
criteria provided, single submitter
|
Jan 4, 2024 | RCV001036748.8 |
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
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
(Jan 04, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001200126.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1685 of the RIMS1 protein (p.Thr1685Ala). … (more)
This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1685 of the RIMS1 protein (p.Thr1685Ala). This variant is present in population databases (rs200035429, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RIMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 835781). 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 tolerated. 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)
|
|
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not provided
(-)
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no classification provided
Method: phenotyping only
|
Not Provided
Affected status: unknown
Allele origin:
unknown
|
GenomeConnect - Invitae Patient Insights Network
Accession: SCV001749863.1
First in ClinVar: Jul 18, 2021 Last updated: Jul 18, 2021 |
Comment:
Variant interpreted as Uncertain significance and reported on 01-24-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided … (more)
Variant interpreted as Uncertain significance and reported on 01-24-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. (less)
Clinical Features:
Abnormal lens morphology (present) , Abnormality of vision (present) , Myopia (present) , Abnormal retinal morphology (present) , Asthma (present) , Autoimmunity (present) , Hypogonadism … (more)
Abnormal lens morphology (present) , Abnormality of vision (present) , Myopia (present) , Abnormal retinal morphology (present) , Asthma (present) , Autoimmunity (present) , Hypogonadism (present) (less)
Indication for testing: Diagnostic
Age: 70-79 years
Sex: female
Testing laboratory: Invitae
Date variant was reported to submitter: 2020-01-24
Testing laboratory interpretation: Uncertain significance
|
Comment:
Comment:
Variant interpreted as Uncertain significance and reported on 01-24-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.
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 sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1685 of the RIMS1 protein (p.Thr1685Ala). This variant is present in population databases (rs200035429, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RIMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 835781). 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 tolerated. 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.
Comment:
Variant interpreted as Uncertain significance and reported on 01-24-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs200035429 ...
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.