ClinVar Genomic variation as it relates to human health
NM_000539.3(RHO):c.316G>A (p.Gly106Arg)
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_000539.3(RHO):c.316G>A (p.Gly106Arg)
Variation ID: 13038 Accession: VCV000013038.13
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3q22.1 3: 129529049 (GRCh38) [ NCBI UCSC ] 3: 129247892 (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 Oct 23, 2017 Mar 10, 2024 Nov 13, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000539.3:c.316G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000530.1:p.Gly106Arg missense NC_000003.12:g.129529049G>A NC_000003.11:g.129247892G>A NG_009115.1:g.5411G>A P08100:p.Gly106Arg - Protein change
- G106R
- Other names
- NP_000530.1:p.(Gly106Arg)
- Canonical SPDI
- NC_000003.12:129529048: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
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00002
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
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. |
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RHO | - | - |
GRCh38 GRCh37 |
580 | 595 |
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
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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/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Apr 8, 2021 | RCV000013913.28 | |
Pathogenic (2) |
criteria provided, single submitter
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Jul 24, 2023 | RCV000787679.2 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Oct 1, 2023 | RCV001074389.4 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Nov 13, 2023 | RCV001207877.9 |
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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Likely pathogenic
(Sep 01, 2020)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 4
Affected status: yes
Allele origin:
germline
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Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals
Accession: SCV001443208.1
First in ClinVar: Nov 19, 2020 Last updated: Nov 19, 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 4
Affected status: yes
Allele origin:
germline
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Ocular Genomics Institute, Massachusetts Eye and Ear
Accession: SCV001573345.1
First in ClinVar: May 10, 2021 Last updated: May 10, 2021 |
Comment:
The RHO c.316G>A variant was identified in an individual with retinitis pigmentosa with a presumed dominant inheritance pattern. Through a review of available evidence we … (more)
The RHO c.316G>A 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: PM2, PP3, PP1-S, PS3. Based on this evidence we have classified this variant as Pathogenic. (less)
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Pathogenic
(Aug 06, 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: SCV001239967.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020
Comment:
My Retina Tracker patient
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Pathogenic
(Jun 17, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001762263.1
First in ClinVar: Jul 30, 2021 Last updated: Jul 30, 2021 |
Clinical Features:
Rod-cone dystrophy (present) , Cone-rod dystrophy (present) , Sectoral retinitis pigmentosa (present)
Sex: male
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Pathogenic
(Jul 24, 2023)
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criteria provided, single submitter
Method: research
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Retinitis pigmentosa
Affected status: yes
Allele origin:
germline
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Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel
Accession: SCV004030291.1
First in ClinVar: Sep 03, 2023 Last updated: Sep 03, 2023
Comment:
This variant was classified as Pathogenic based on ACMG criteria: PS1, PM2, PM5, PM1, PP3, PP2, PP5.
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Comment:
Clinical significance based on ACMG v2.0
Number of individuals with the variant: 2
Sex: mixed
Geographic origin: Portugal
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Pathogenic
(Nov 13, 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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001379244.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 106 of the RHO protein (p.Gly106Arg). … (more)
This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 106 of the RHO protein (p.Gly106Arg). This variant is present in population databases (rs104893773, gnomAD 0.01%). This missense change has been observed in individuals with autosomal dominant retinitis pigmentosa (PMID: 1301135, 8905849, 11094174, 28559085). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 13038). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RHO protein function with a positive predictive value of 80%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on RHO function (PMID: 24520188). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(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: SCV004705651.1
First in ClinVar: Mar 10, 2024 Last updated: Mar 10, 2024 |
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Pathogenic
(Aug 01, 1993)
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no assertion criteria provided
Method: literature only
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RETINITIS PIGMENTOSA 4
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000034160.2
First in ClinVar: Apr 04, 2013 Last updated: Oct 23, 2017 |
Comment on evidence:
In a family with autosomal dominant RP (RP4; 613731), Inglehearn et al. (1992) found a GGG-to-AGG mutation at codon 106 of the RHO gene, resulting … (more)
In a family with autosomal dominant RP (RP4; 613731), Inglehearn et al. (1992) found a GGG-to-AGG mutation at codon 106 of the RHO gene, resulting in substitution of arginine for glycine (G106R). Fishman et al. (1992) found a gly106-to-arg mutation in the RHO gene in 3 members of one family and in 1 person of another family. All affected persons had a distinctive phenotype that included a regional predilection for pigmentary changes to occur in the inferior retina as well as visual field impairment predominantly in the superior hemisphere. Substantial residual electroretinographic amplitudes with normal implicit times were also consistent with a form of 'sector' retinitis pigmentosa. Thus the specific mutation appears to be associated with a better visual prognosis. (less)
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Pathogenic
(Apr 01, 2018)
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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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Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet
Study: VeluxRD
Accession: SCV000926669.2 First in ClinVar: Jul 21, 2019 Last updated: Sep 03, 2023 |
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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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The first genetic landscape of inherited retinal dystrophies in Portuguese patients identifies recurrent homozygous mutations as a frequent cause of pathogenesis. | Peter VG | PNAS nexus | 2023 | PMID: 36909829 |
Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy. | Jespersgaard C | Scientific reports | 2019 | PMID: 30718709 |
Clinically Focused Molecular Investigation of 1000 Consecutive Families with Inherited Retinal Disease. | Stone EM | Ophthalmology | 2017 | PMID: 28559085 |
Assessing the correlation between mutant rhodopsin stability and the severity of retinitis pigmentosa. | McKeone R | Molecular vision | 2014 | PMID: 24520188 |
Rhodopsin gene codon 106 mutation (Gly-to-Arg) in a Japanese family with autosomal dominant retinitis pigmentosa. | Budu | Japanese journal of ophthalmology | 2000 | PMID: 11094174 |
G106R rhodopsin mutation is also present in Spanish ADRP patients. | Ayuso C | Ophthalmic genetics | 1996 | PMID: 8905849 |
Evidence against a second autosomal dominant retinitis pigmentosa locus close to rhodopsin on chromosome 3q. | Inglehearn C | American journal of human genetics | 1993 | PMID: 8328469 |
Ocular findings associated with a rhodopsin gene codon 106 mutation. Glycine-to-arginine change in autosomal dominant retinitis pigmentosa. | Fishman GA | Archives of ophthalmology (Chicago, Ill. : 1960) | 1992 | PMID: 1580841 |
A completed screen for mutations of the rhodopsin gene in a panel of patients with autosomal dominant retinitis pigmentosa. | Inglehearn CF | Human molecular genetics | 1992 | PMID: 1301135 |
Text-mined citations for rs104893773 ...
HelpRecord last updated Oct 13, 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.