NM_001034853.2:c.3060_3071delAGTGGAAGGGGA

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBA1

The NM_001034853.2(RPGR):c.3060_3071delAGTGGAAGGGGA(p.Val1021_Glu1024del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.074 in 1,110,662 control chromosomes in the GnomAD database, including 2,635 homozygotes. There are 24,066 hemizygotes in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 119 hom., 339 hem., cov: 0)

Exomes 𝑓: 0.076 ( 2516 hom. 23727 hem. )

Consequence

RPGR
NM_001034853.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.627

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 -14 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001034853.2.

BP6

Variant X-38285927-CTCCCCTTCCACT-C is Benign according to our data. Variant chrX-38285927-CTCCCCTTCCACT-C is described in ClinVar as Benign. ClinVar VariationId is 403391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0713 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034853.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RPGR	NM_001034853.2	MANE Select	c.3060_3071delAGTGGAAGGGGA	p.Val1021_Glu1024del	disruptive_inframe_deletion	Exon 15 of 15	NP_001030025.1
RPGR	NM_000328.3		c.1905+1155_1905+1166delAGTGGAAGGGGA		intron	N/A	NP_000319.1
RPGR	NM_001367245.1		c.1902+1155_1902+1166delAGTGGAAGGGGA		intron	N/A	NP_001354174.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RPGR	ENST00000645032.1	MANE Select	c.3060_3071delAGTGGAAGGGGA	p.Val1021_Glu1024del	disruptive_inframe_deletion	Exon 15 of 15	ENSP00000495537.1
ENSG00000250349	ENST00000465127.1	TSL:5	c.172-380184_172-380173delACTTCCCCTTCC		intron	N/A	ENSP00000417050.1
RPGR	ENST00000339363.7	TSL:5	c.2520+1155_2520+1166delAGTGGAAGGGGA		intron	N/A	ENSP00000343671.3

Frequencies

GnomAD3 genomes

AF:

0.0474

AC:

4077

AN:

85926

Hom.:

119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0160

Gnomad AMI

AF:

0.0139

Gnomad AMR

AF:

0.0299

Gnomad ASJ

AF:

0.0608

Gnomad EAS

AF:

0.000371

Gnomad SAS

AF:

0.0199

Gnomad FIN

AF:

0.0300

Gnomad MID

AF:

0.0335

Gnomad NFE

AF:

0.0734

Gnomad OTH

AF:

0.0446

GnomAD2 exomes

AF:

0.0524

AC:

6503

AN:

123985

AF XY:

0.0500

show subpopulations

Gnomad AFR exome

AF:

0.0193

Gnomad AMR exome

AF:

0.0341

Gnomad ASJ exome

AF:

0.0643

Gnomad EAS exome

AF:

0.000404

Gnomad FIN exome

AF:

0.0581

Gnomad NFE exome

AF:

0.0813

Gnomad OTH exome

AF:

0.0582

GnomAD4 exome

AF:

0.0763

AC:

78159

AN:

1024694

Hom.:

2516

AF XY:

0.0723

AC XY:

23727

AN XY:

328400

show subpopulations

African (AFR)

AF:

0.0202

AC:

511

AN:

25297

American (AMR)

AF:

0.0368

AC:

1091

AN:

29657

Ashkenazi Jewish (ASJ)

AF:

0.0681

AC:

1220

AN:

17911

East Asian (EAS)

AF:

0.000248

AC:

AN:

28252

South Asian (SAS)

AF:

0.0298

AC:

1505

AN:

50550

European-Finnish (FIN)

AF:

0.0708

AC:

2247

AN:

31747

Middle Eastern (MID)

AF:

0.0807

AC:

305

AN:

3781

European-Non Finnish (NFE)

AF:

0.0858

AC:

68151

AN:

794047

Other (OTH)

AF:

0.0718

AC:

3122

AN:

43452

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.405

Heterozygous variant carriers

2232

4464

6696

8928

11160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2438

4876

7314

9752

12190

<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:

0.0474

AC:

4076

AN:

85968

Hom.:

119

Cov.:

AF XY:

0.0199

AC XY:

339

AN XY:

17014

show subpopulations

African (AFR)

AF:

0.0159

AC:

371

AN:

23282

American (AMR)

AF:

0.0298

AC:

235

AN:

7888

Ashkenazi Jewish (ASJ)

AF:

0.0608

AC:

129

AN:

2120

East Asian (EAS)

AF:

0.000372

AC:

AN:

2685

South Asian (SAS)

AF:

0.0199

AC:

AN:

1405

European-Finnish (FIN)

AF:

0.0300

AC:

125

AN:

4165

Middle Eastern (MID)

AF:

0.0359

AC:

AN:

167

European-Non Finnish (NFE)

AF:

0.0734

AC:

3123

AN:

42542

Other (OTH)

AF:

0.0439

AC:

AN:

1140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

152

304

457

609

761

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0642

Hom.:

444

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.63

Mutation Taster

=191/9

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over