X-38286776-C-T

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.2223G>A(p.Glu741Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.064 in 1,151,088 control chromosomes in the GnomAD database, including 2,387 homozygotes. There are 23,492 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 472 hom., 1748 hem., cov: 16)

Exomes 𝑓: 0.062 ( 1915 hom. 21744 hem. )

Consequence

RPGR
NM_001034853.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.27

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant X-38286776-C-T is Benign according to our data. Variant chrX-38286776-C-T is described in ClinVar as Benign. ClinVar VariationId is 257192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.27 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGR	NM_001034853.2 link	c.2223G>A	p.Glu741Glu	synonymous_variant	Exon 15 of 15	ENST00000645032.1	NP_001030025.1	Q92834-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPGR	ENST00000645032.1 link	c.2223G>A	p.Glu741Glu	synonymous_variant	Exon 15 of 15		NM_001034853.2	ENSP00000495537.1		Q92834-6
ENSG00000250349	ENST00000465127.1 link	c.172-379345C>T		intron_variant	Intron 3 of 8	5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

AF:

0.0890

AC:

8749

AN:

98349

Hom.:

474

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.0680

Gnomad EAS

AF:

0.0656

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.0831

Gnomad MID

AF:

0.0524

Gnomad NFE

AF:

0.0485

Gnomad OTH

AF:

0.0719

GnomAD2 exomes

AF:

0.107

AC:

12101

AN:

113559

AF XY:

0.101

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.221

Gnomad ASJ exome

AF:

0.0627

Gnomad EAS exome

AF:

0.0673

Gnomad FIN exome

AF:

0.0978

Gnomad NFE exome

AF:

0.0472

Gnomad OTH exome

AF:

0.0750

GnomAD4 exome

AF:

0.0617

AC:

64904

AN:

1052703

Hom.:

1915

Cov.:

AF XY:

0.0633

AC XY:

21744

AN XY:

343527

show subpopulations

African (AFR)

AF:

0.167

AC:

4156

AN:

24915

American (AMR)

AF:

0.207

AC:

5777

AN:

27894

Ashkenazi Jewish (ASJ)

AF:

0.0607

AC:

1124

AN:

18526

East Asian (EAS)

AF:

0.0789

AC:

2145

AN:

27200

South Asian (SAS)

AF:

0.147

AC:

7293

AN:

49615

European-Finnish (FIN)

AF:

0.0915

AC:

3437

AN:

37543

Middle Eastern (MID)

AF:

0.0638

AC:

227

AN:

3560

European-Non Finnish (NFE)

AF:

0.0461

AC:

37798

AN:

819089

Other (OTH)

AF:

0.0664

AC:

2947

AN:

44361

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

2321

4641

6962

9282

11603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1636

3272

4908

6544

8180

<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:

0.0890

AC:

8754

AN:

98385

Hom.:

472

Cov.:

AF XY:

0.0767

AC XY:

1748

AN XY:

22795

show subpopulations

African (AFR)

AF:

0.152

AC:

4021

AN:

26405

American (AMR)

AF:

0.129

AC:

1129

AN:

8782

Ashkenazi Jewish (ASJ)

AF:

0.0680

AC:

166

AN:

2440

East Asian (EAS)

AF:

0.0658

AC:

204

AN:

3100

South Asian (SAS)

AF:

0.133

AC:

245

AN:

1844

European-Finnish (FIN)

AF:

0.0831

AC:

395

AN:

4752

Middle Eastern (MID)

AF:

0.0479

AC:

AN:

188

European-Non Finnish (NFE)

AF:

0.0485

AC:

2376

AN:

48965

Other (OTH)

AF:

0.0703

AC:

AN:

1323

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

269

539

808

1078

1347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<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:

0.105

Hom.:

877

Bravo

AF:

0.103

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 -

not provided

Benign:2

Jul 12, 2018

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

- -

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

-0.79

CADD

Benign

1.0

(source)

DANN

Benign

0.43

PhyloP100

-2.3

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