rs5963403

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001034853.2(RPGR):c.552G>T(p.Gln184His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0037 in 1,205,773 control chromosomes in the GnomAD database, including 100 homozygotes. There are 1,194 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.020 ( 46 hom., 604 hem., cov: 23)

Exomes 𝑓: 0.0021 ( 54 hom. 590 hem. )

Consequence

RPGR
NM_001034853.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0120

Publications

4 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029917061).

BP6

Variant X-38317383-C-A is Benign according to our data. Variant chrX-38317383-C-A is described in ClinVar as Benign. ClinVar VariationId is 255836.Status of the report is reviewed_by_expert_panel, 3 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGR	NM_001034853.2 link	c.552G>T	p.Gln184His	missense_variant	Exon 6 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.552G>T	p.Gln184His	missense_variant	Exon 6 of 15		NM_001034853.2	ENSP00000495537.1
ENSG00000250349	ENST00000465127.1 link	c.172-348738C>A		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

Frequencies

GnomAD3 genomes

AF:

0.0197

AC:

2201

AN:

111501

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0687

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00747

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000375

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000113

Gnomad OTH

AF:

0.0106

GnomAD2 exomes

AF:

0.00568

AC:

1041

AN:

183202

AF XY:

0.00359

show subpopulations

Gnomad AFR exome

AF:

0.0717

Gnomad AMR exome

AF:

0.00281

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000856

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00205

AC:

2246

AN:

1094221

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

590

AN XY:

359739

show subpopulations

African (AFR)

AF:

0.0701

AC:

1846

AN:

26319

American (AMR)

AF:

0.00341

AC:

120

AN:

35182

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19368

East Asian (EAS)

AF:

0.00

AC:

AN:

30179

South Asian (SAS)

AF:

0.000222

AC:

AN:

54016

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40522

Middle Eastern (MID)

AF:

0.00145

AC:

AN:

4126

European-Non Finnish (NFE)

AF:

0.0000477

AC:

AN:

838517

Other (OTH)

AF:

0.00483

AC:

222

AN:

45992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

166

248

331

414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<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:

0.0198

AC:

2211

AN:

111552

Hom.:

Cov.:

AF XY:

0.0179

AC XY:

604

AN XY:

33760

show subpopulations

African (AFR)

AF:

0.0689

AC:

2110

AN:

30638

American (AMR)

AF:

0.00746

AC:

AN:

10449

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3561

South Asian (SAS)

AF:

0.000376

AC:

AN:

2662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6027

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.000113

AC:

AN:

53139

Other (OTH)

AF:

0.0105

AC:

AN:

1523

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

140

210

280

350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00677

Hom.:

366

Bravo

AF:

0.0229

ESP6500AA

AF:

0.0730

AC:

280

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00622

AC:

755

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 01, 2015

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:2

Feb 04, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

X-linked cone-rod dystrophy 1;C1845667:Retinitis pigmentosa 3;C2749137:Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness;C3151784:Macular degeneration, X-linked atrophic

Benign:1

Apr 08, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.65

CADD

Benign

1.3

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.17

.;.;T;.;.;.;.;.;.

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.47

.;T;T;T;T;.;T;T;T

MetaRNN

Benign

0.0030

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.5

L;L;L;.;L;L;L;.;.

PhyloP100

0.012

PrimateAI

Benign

0.29

PROVEAN

Benign

0.90

N;.;N;.;.;.;N;.;.

REVEL

Benign

0.17

Sift

Benign

0.85

T;.;T;.;.;.;.;.;.

Sift4G

Benign

0.35

T;.;T;.;.;.;T;.;.

Polyphen

0.0020

B;B;.;.;.;.;.;.;.

Vest4

0.14

MutPred

0.60

Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);.;Gain of sheet (P = 0.1208);

MVP

0.39

MPC

0.69

ClinPred

0.0015

GERP RS

-3.5

Varity_R

0.16

gMVP

0.50

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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