VCV000100560.26 - ClinVar

NM_001034853.2(RPGR):c.223A>G (p.Ile75Val)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign/Likely benign

9 out of 11 submissions contributed to this classification

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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001034853.2(RPGR):c.223A>G (p.Ile75Val)

Variation ID: 100560 Accession: VCV000100560.26

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xp11.4 X: 38322877 (GRCh38) [ NCBI UCSC ] X: 38182130 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	Feb 25, 2014	Apr 13, 2025	Feb 3, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001034853.2:c.223A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001030025.1:p.Ile75Val	missense
NM_000328.3:c.223A>G	NP_000319.1:p.Ile75Val	missense
NM_001367245.1:c.223A>G	NP_001354174.1:p.Ile75Val	missense
NM_001367246.1:c.223A>G	NP_001354175.1:p.Ile75Val	missense
NM_001367247.1:c.223A>G	NP_001354176.1:p.Ile75Val	missense
NM_001367248.1:c.253A>G	NP_001354177.1:p.Ile85Val	missense
NM_001367249.1:c.223A>G	NP_001354178.1:p.Ile75Val	missense
NM_001367250.1:c.223A>G	NP_001354179.1:p.Ile75Val	missense
NM_001367251.1:c.223A>G	NP_001354180.1:p.Ile75Val	missense
NR_159803.1:n.365A>G		non-coding transcript variant
NR_159804.1:n.365A>G		non-coding transcript variant
NR_159805.1:n.365A>G		non-coding transcript variant
NR_159806.1:n.365A>G		non-coding transcript variant
NR_159807.1:n.365A>G		non-coding transcript variant
NR_159808.1:n.633A>G		non-coding transcript variant
NC_000023.11:g.38322877T>C
NC_000023.10:g.38182130T>C
NG_009553.1:g.9659A>G
	Q92834:p.Ile75Val

... more HGVS ... less HGVS

Protein change

I75V, I85V

Other names

Canonical SPDI

NC_000023.11:38322876:T:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

0.02543 (C)

Allele frequency Help The frequency of the allele represented by this VCV record.

Trans-Omics for Precision Medicine (TOPMed) 0.03568

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.03825

The Genome Aggregation Database (gnomAD), exomes 0.01586

Exome Aggregation Consortium (ExAC) 0.01754

1000 Genomes Project 0.02543

1000 Genomes Project 30x 0.02914

The Genome Aggregation Database (gnomAD) 0.03363

Links

ClinGen: CA202241 UniProtKB: Q92834#VAR_008503 dbSNP: rs111631988 VarSome

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
Gene	OMIM	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.
RPGR		-	-	GRCh38 GRCh37	1723	1899

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.
not provided	Benign/Likely benign (5)	criteria provided, multiple submitters, no conflicts	Nov 27, 2019	RCV000086937.11
not specified	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Jan 11, 2022	RCV000177042.10
Primary ciliary dyskinesia	Benign (2)	criteria provided, multiple submitters, no conflicts	Feb 3, 2025	RCV000474670.14
Macular degeneration, X-linked atrophic Retinitis pigmentosa 3 Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness X-linked cone-rod dystrophy 1	Benign (1)	criteria provided, single submitter	Nov 9, 2021	RCV002498471.2

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 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.
Benign (May 13, 2015) C Contributing to aggregate classification	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000228854.6 First in ClinVar: Jun 28, 2015 Last updated: Apr 13, 2025	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=RPGR Number of individuals with the variant: 1 Zygosity: Single Heterozygote Sex: mixed
Benign (Jan 13, 2015) C Contributing to aggregate classification	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000269758.3 First in ClinVar: May 29, 2016 Last updated: May 29, 2016	Comment: p.Ile75Val in exon 3 of RPGR: This variant is not expected to have clinical sign ificance because it has been identified in 8.9% (343/3833) of … (more) p.Ile75Val in exon 3 of RPGR: This variant is not expected to have clinical sign ificance because it has been identified in 8.9% (343/3833) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs111631988). (less) Number of individuals with the variant: 6
Benign (Feb 03, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Primary ciliary dyskinesia Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000557300.8 First in ClinVar: Apr 17, 2017 Last updated: Feb 25, 2025
Benign (Jul 09, 2018) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001950986.2 First in ClinVar: Oct 02, 2021 Last updated: Mar 04, 2023	Comment: This variant is associated with the following publications: (PMID: 22995991, 22025579, 9399904, 27884173)
Likely benign (Jan 11, 2022) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV002074202.1 First in ClinVar: Feb 12, 2022 Last updated: Feb 12, 2022
Benign (Dec 01, 2014) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Primary ciliary dyskinesia Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV002727944.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Comment: This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more) This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Benign (Nov 27, 2019) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV002759503.1 First in ClinVar: Dec 11, 2022 Last updated: Dec 11, 2022
Benign (Nov 09, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Retinitis pigmentosa 3 Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness Macular degeneration, X-linked atrophic X-linked cone-rod dystrophy 1 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002808043.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Likely benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (X-linked inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005209240.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
probable-non-pathogenic (-) N Not contributing to aggregate classification	no assertion criteria provided Method: not provided	not provided Affected status: not provided Allele origin: not provided	Department of Ophthalmology and Visual Sciences Kyoto University Accession: SCV000172560.1 First in ClinVar: Aug 08, 2014 Last updated: Aug 08, 2014	Comment: Converted during submission to Likely benign.
not provided (-) N Not contributing to aggregate classification	no classification provided Method: not provided	not provided Affected status: not provided Allele origin: not provided	NEI Ophthalmic Genomics Laboratory, National Institutes of Health Accession: SCV000119189.1 First in ClinVar: Feb 25, 2014 Last updated: Feb 25, 2014
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Comment:

p.Ile75Val in exon 3 of RPGR: This variant is not expected to have clinical sign ificance because it has been identified in 8.9% (343/3833) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs111631988).

Comment:

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=RPGR	-	-	-	-

Text-mined citations for rs111631988 ...

These 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 Apr 13, 2025

ClinVar Genomic variation as it relates to human health

NM_001034853.2(RPGR):c.223A>G (p.Ile75Val)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs111631988 ...