chrX-38286378-CCTTCCTCCCCTTCTT-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BA1BP3

This summary comes from the ClinGen Evidence Repository: NM_001034853.2(RPGR):c.2606_2620del (p.Glu869_Glu873del) is a short in-frame deletion of 15 nucleotides that encode amino acids 869–873 within a low-complexity region (PMID:27162334) that extends approximately from amino acids 787–1043 in RPGR (BP3). This variant is present in gnomAD v4.1.0 at a frequency of 0.007397 among hemizygous individuals, with 1,400 variant alleles / 189,256 total alleles, which is higher than the ClinGen X-linked IRD VCEP BA1 threshold of >0.00005 (BA1). In summary, this variant is classified as benign for RPGR-related retinopathy based on the ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RPGR Version 1.0.0; BA1 and BP3. (date of approval 05/16/2025). LINK:https://erepo.genome.network/evrepo/ui/classification/CA10385260/MONDO:0100437/106

Frequency

Genomes: 𝑓 0.0035 ( 0 hom., 1 hem., cov: 5)

Exomes 𝑓: 0.0064 ( 53 hom. 1399 hem. )

Failed GnomAD Quality Control

Consequence

RPGR
NM_001034853.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign reviewed by expert panel U:1B:6

Conservation

PhyloP100: 2.04

Publications

1 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 -9 ACMG points.

BP3

For more information check the summary or visit ClinGen Evidence Repository.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGR	NM_001034853.2 link	c.2606_2620delAAGAAGGGGAGGAAG	p.Glu869_Glu873del	disruptive_inframe_deletion	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.2606_2620delAAGAAGGGGAGGAAG	p.Glu869_Glu873del	disruptive_inframe_deletion	Exon 15 of 15		NM_001034853.2	ENSP00000495537.1		Q92834-6
ENSG00000250349	ENST00000465127.1 link	c.172-379741_172-379727delTTCCTCCCCTTCTTC		intron_variant	Intron 3 of 8	5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

AF:

0.00352

AC:

AN:

22175

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000549

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00276

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00514

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000575

AC:

AN:

41741

AF XY:

0.000164

show subpopulations

Gnomad AFR exome

AF:

0.000286

Gnomad AMR exome

AF:

0.000687

Gnomad ASJ exome

AF:

0.000547

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000717

Gnomad NFE exome

AF:

0.000967

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00644

AC:

4453

AN:

690972

Hom.:

AF XY:

0.00743

AC XY:

1399

AN XY:

188180

show subpopulations

African (AFR)

AF:

0.000945

AC:

AN:

15876

American (AMR)

AF:

0.00508

AC:

AN:

14949

Ashkenazi Jewish (ASJ)

AF:

0.0274

AC:

235

AN:

8567

East Asian (EAS)

AF:

0.00

AC:

AN:

11576

South Asian (SAS)

AF:

0.00127

AC:

AN:

33056

European-Finnish (FIN)

AF:

0.0242

AC:

324

AN:

13388

Middle Eastern (MID)

AF:

0.0186

AC:

AN:

1561

European-Non Finnish (NFE)

AF:

0.00611

AC:

3454

AN:

565231

Other (OTH)

AF:

0.0104

AC:

278

AN:

26768

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

127

255

382

510

637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00352

AC:

AN:

22180

Hom.:

Cov.:

AF XY:

0.000929

AC XY:

AN XY:

1076

show subpopulations

African (AFR)

AF:

0.000549

AC:

AN:

5464

American (AMR)

AF:

0.00275

AC:

AN:

1818

Ashkenazi Jewish (ASJ)

AF:

0.00692

AC:

AN:

578

East Asian (EAS)

AF:

0.00

AC:

AN:

638

South Asian (SAS)

AF:

0.00

AC:

AN:

195

European-Finnish (FIN)

AF:

0.00376

AC:

AN:

1063

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00515

AC:

AN:

12049

Other (OTH)

AF:

0.00

AC:

AN:

242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00836

Hom.:

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:6

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not provided

Benign:3

Sep 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

RPGR: BS1, BS2 -

Jul 26, 2017

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 07, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

X-linked cone-rod dystrophy 1

Uncertain:1

Jan 01, 2021

DBGen Ocular Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Class 3 ACMG Guidelines, 2015 -

not specified

Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

RPGR-related retinopathy

Benign:1

May 20, 2025

ClinGen X-linked Inherited Retinal Disease Variant Curation Expert Panel, ClinGen

Significance:Benign

Review Status:reviewed by expert panel

Collection Method:curation

NM_001034853.2(RPGR):c.2606_2620del (p.Glu869_Glu873del) is a short in-frame deletion of 15 nucleotides that encode amino acids 869–873 within a low-complexity region (PMID: 27162334) that extends approximately from amino acids 787–1043 in RPGR (BP3). This variant is present in gnomAD v4.1.0 at a frequency of 0.007397 among hemizygous individuals, with 1,400 variant alleles / 189,256 total alleles, which is higher than the ClinGen X-linked IRD VCEP BA1 threshold of >0.00005 (BA1). In summary, this variant is classified as benign for RPGR-related retinopathy based on the ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RPGR Version 1.0.0; BA1 and BP3. (date of approval 05/16/2025). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.0

Mutation Taster

=200/0

polymorphism

(source)

Splicing

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