rs111787313

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001034853.2(RPGR):c.3219C>T(p.Gly1073Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 1,205,849 control chromosomes in the GnomAD database, including 1,654 homozygotes. There are 16,653 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 286 hom., 2046 hem., cov: 21)

Exomes 𝑓: 0.038 ( 1368 hom. 14607 hem. )

Consequence

RPGR
NM_001034853.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.55

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

retinitis pigmentosa 3
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
RPGR-related retinopathy
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
primary ciliary dyskinesia-retinitis pigmentosa syndrome
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
macular degeneration, X-linked atrophic
Inheritance: XL Classification: LIMITED Submitted by: G2P

RPGR links:

ENSG00000250349 (HGNC:):

ENSG00000250349 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant X-38285780-G-A is Benign according to our data. Variant chrX-38285780-G-A is described in ClinVar as Benign. ClinVar VariationId is 403390.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.55 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGR	NM_001034853.2 link	c.3219C>T	p.Gly1073Gly	synonymous_variant	Exon 15 of 15	ENST00000645032.1	NP_001030025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPGR	ENST00000645032.1 link	c.3219C>T	p.Gly1073Gly	synonymous_variant	Exon 15 of 15		NM_001034853.2	ENSP00000495537.1
ENSG00000250349	ENST00000465127.1 link	c.172-380341G>A		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

Frequencies

GnomAD3 genomes

AF:

0.0644

AC:

6956

AN:

107954

Hom.:

287

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.0250

Gnomad EAS

AF:

0.0728

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.0812

Gnomad MID

AF:

0.0173

Gnomad NFE

AF:

0.0202

Gnomad OTH

AF:

0.0557

GnomAD2 exomes

AF:

0.0800

AC:

14513

AN:

181522

AF XY:

0.0722

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.217

Gnomad ASJ exome

AF:

0.0191

Gnomad EAS exome

AF:

0.0697

Gnomad FIN exome

AF:

0.0761

Gnomad NFE exome

AF:

0.0200

Gnomad OTH exome

AF:

0.0439

GnomAD4 exome

AF:

0.0379

AC:

41559

AN:

1097849

Hom.:

1368

Cov.:

AF XY:

0.0402

AC XY:

14607

AN XY:

363293

show subpopulations

African (AFR)

AF:

0.129

AC:

3409

AN:

26395

American (AMR)

AF:

0.203

AC:

7150

AN:

35197

Ashkenazi Jewish (ASJ)

AF:

0.0192

AC:

372

AN:

19381

East Asian (EAS)

AF:

0.0784

AC:

2367

AN:

30204

South Asian (SAS)

AF:

0.144

AC:

7773

AN:

54142

European-Finnish (FIN)

AF:

0.0697

AC:

2816

AN:

40392

Middle Eastern (MID)

AF:

0.0251

AC:

104

AN:

4137

European-Non Finnish (NFE)

AF:

0.0186

AC:

15697

AN:

841920

Other (OTH)

AF:

0.0406

AC:

1871

AN:

46081

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

1593

3187

4780

6374

7967

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

858

1716

2574

3432

4290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0645

AC:

6963

AN:

108000

Hom.:

286

Cov.:

AF XY:

0.0664

AC XY:

2046

AN XY:

30792

show subpopulations

African (AFR)

AF:

0.121

AC:

3584

AN:

29560

American (AMR)

AF:

0.112

AC:

1127

AN:

10094

Ashkenazi Jewish (ASJ)

AF:

0.0250

AC:

AN:

2602

East Asian (EAS)

AF:

0.0731

AC:

251

AN:

3436

South Asian (SAS)

AF:

0.145

AC:

352

AN:

2422

European-Finnish (FIN)

AF:

0.0812

AC:

448

AN:

5520

Middle Eastern (MID)

AF:

0.0145

AC:

AN:

207

European-Non Finnish (NFE)

AF:

0.0202

AC:

1053

AN:

52012

Other (OTH)

AF:

0.0543

AC:

AN:

1472

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

221

441

662

882

1103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0337

Hom.:

331

Bravo

AF:

0.0728

EpiCase

AF:

0.0180

EpiControl

AF:

0.0175

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 03, 2018

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Primary ciliary dyskinesia

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinal dystrophy

Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.11

(source)

DANN

Benign

0.70

PhyloP100

-3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over