rs1801686
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001034853.2(RPGR):c.1164G>A(p.Ala388=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,209,105 control chromosomes in the GnomAD database, including 9,112 homozygotes. There are 54,798 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.12 ( 665 hom., 3599 hem., cov: 23)
Exomes 𝑓: 0.14 ( 8447 hom. 51199 hem. )
Consequence
RPGR
NM_001034853.2 synonymous
NM_001034853.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.21
Genes affected
RPGR (HGNC:10295): (retinitis pigmentosa GTPase regulator) This gene encodes a protein with a series of six RCC1-like domains (RLDs), characteristic of the highly conserved guanine nucleotide exchange factors. The encoded protein is found in the Golgi body and interacts with RPGRIP1. This protein localizes to the outer segment of rod photoreceptors and is essential for their viability. Mutations in this gene have been associated with X-linked retinitis pigmentosa (XLRP). Multiple alternatively spliced transcript variants that encode different isoforms of this gene have been reported, but the full-length natures of only some have been determined. [provided by RefSeq, Dec 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
Variant X-38299037-C-T is Benign according to our data. Variant chrX-38299037-C-T is described in ClinVar as [Benign]. Clinvar id is 92849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38299037-C-T is described in Lovd as [Likely_benign]. Variant chrX-38299037-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-2.21 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPGR | NM_001034853.2 | c.1164G>A | p.Ala388= | synonymous_variant | 10/15 | ENST00000645032.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPGR | ENST00000645032.1 | c.1164G>A | p.Ala388= | synonymous_variant | 10/15 | NM_001034853.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.116 AC: 12869AN: 111305Hom.: 665 Cov.: 23 AF XY: 0.107 AC XY: 3597AN XY: 33533
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GnomAD3 exomes AF: 0.109 AC: 19982AN: 182902Hom.: 928 AF XY: 0.110 AC XY: 7409AN XY: 67414
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GnomAD4 exome AF: 0.144 AC: 158323AN: 1097749Hom.: 8447 Cov.: 31 AF XY: 0.141 AC XY: 51199AN XY: 363171
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GnomAD4 genome ? AF: 0.116 AC: 12866AN: 111356Hom.: 665 Cov.: 23 AF XY: 0.107 AC XY: 3599AN XY: 33594
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ClinVar
Significance: Benign
Submissions summary: Benign:10Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 02, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 03, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 11, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 13, 2015 | p.Ala388Ala in exon 10 of RPGR: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 15.5% (1041/6728) of European American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1801686). - |
Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 10, 2014 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Retinitis pigmentosa 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Macular degeneration, X-linked atrophic Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
X-linked cone-rod dystrophy 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
not provided Other:1
not provided, no classification provided | literature only | Retina International | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at