rs1801686

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10O:1

Conservation

PhyloP100: -2.21

Variant links:

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]

RPGR links:

Genome browser will be placed here

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 linkuse as main transcript	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 linkuse as main transcript	c.1164G>A	p.Ala388=	synonymous_variant	10/15		NM_001034853.2	A2	Q92834-6

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

12869

AN:

111305

Hom.:

665

Cov.:

AF XY:

0.107

AC XY:

3597

AN XY:

33533

show subpopulations

Gnomad AFR

AF:

0.0674

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.0785

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.000557

Gnomad SAS

AF:

0.0335

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.151

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.104

GnomAD3 exomes

AF:

0.109

AC:

19982

AN:

182902

Hom.:

928

AF XY:

0.110

AC XY:

7409

AN XY:

67414

show subpopulations

Gnomad AFR exome

AF:

0.0657

Gnomad AMR exome

AF:

0.0468

Gnomad ASJ exome

AF:

0.129

Gnomad EAS exome

AF:

0.000361

Gnomad SAS exome

AF:

0.0357

Gnomad FIN exome

AF:

0.172

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.144

AC:

158323

AN:

1097749

Hom.:

8447

Cov.:

AF XY:

0.141

AC XY:

51199

AN XY:

363171

show subpopulations

Gnomad4 AFR exome

AF:

0.0649

Gnomad4 AMR exome

AF:

0.0500

Gnomad4 ASJ exome

AF:

0.126

Gnomad4 EAS exome

AF:

0.000464

Gnomad4 SAS exome

AF:

0.0383

Gnomad4 FIN exome

AF:

0.176

Gnomad4 NFE exome

AF:

0.162

Gnomad4 OTH exome

AF:

0.130

GnomAD4 genome

AF:

0.116

AC:

12866

AN:

111356

Hom.:

665

Cov.:

AF XY:

0.107

AC XY:

3599

AN XY:

33594

show subpopulations

Gnomad4 AFR

AF:

0.0673

Gnomad4 AMR

AF:

0.0784

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.000559

Gnomad4 SAS

AF:

0.0336

Gnomad4 FIN

AF:

0.162

Gnomad4 NFE

AF:

0.157

Gnomad4 OTH

AF:

0.102

Alfa

AF:

0.137

Hom.:

1590

Bravo

AF:

0.107

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	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	Eurofins Ntd Llc (ga)	Jan 02, 2013	- -
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). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
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. -

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

Cadd

Benign

0.50

Dann

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over