NM_001034853.2:c.1059+25T>C

Variant names:

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.1059+25T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 1,157,980 control chromosomes in the GnomAD database, including 1,207 homozygotes. There are 13,490 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 92 hom., 1209 hem., cov: 22)

Exomes 𝑓: 0.034 ( 1115 hom. 12281 hem. )

Consequence

RPGR
NM_001034853.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.684

Publications

2 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), PanelApp Australia
RPGR-related retinopathy
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
primary ciliary dyskinesia-retinitis pigmentosa syndrome
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
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 (BayesDel_noAF=-0.77).

BP6

Variant X-38301222-A-G is Benign according to our data. Variant chrX-38301222-A-G is described in ClinVar as Benign. ClinVar VariationId is 257191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.129 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	Effect	Exon Rank	Protein	UniProt
RPGR	NM_001034853.2	MANE Select	c.1059+25T>C	intron	N/A	NP_001030025.1	Q92834-6
RPGR	NM_000328.3		c.1059+25T>C	intron	N/A	NP_000319.1	Q92834-2
RPGR	NM_001367245.1		c.1056+25T>C	intron	N/A	NP_001354174.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPGR	ENST00000645032.1	MANE Select	c.1059+25T>C	intron	N/A	ENSP00000495537.1	Q92834-6
ENSG00000250349	ENST00000465127.1	TSL:5	c.172-364899A>G	intron	N/A	ENSP00000417050.1	B4E171
RPGR	ENST00000494841.1	TSL:1	n.322+25T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0312

AC:

3480

AN:

111660

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00861

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0939

Gnomad ASJ

AF:

0.0257

Gnomad EAS

AF:

0.0723

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.0734

Gnomad MID

AF:

0.0169

Gnomad NFE

AF:

0.0196

Gnomad OTH

AF:

0.0353

GnomAD2 exomes

AF:

0.0712

AC:

11344

AN:

159227

AF XY:

0.0669

show subpopulations

Gnomad AFR exome

AF:

0.00854

Gnomad AMR exome

AF:

0.213

Gnomad ASJ exome

AF:

0.0189

Gnomad EAS exome

AF:

0.0701

Gnomad FIN exome

AF:

0.0752

Gnomad NFE exome

AF:

0.0193

Gnomad OTH exome

AF:

0.0387

GnomAD4 exome

AF:

0.0342

AC:

35808

AN:

1046264

Hom.:

1115

Cov.:

AF XY:

0.0378

AC XY:

12281

AN XY:

324502

show subpopulations

African (AFR)

AF:

0.00837

AC:

210

AN:

25099

American (AMR)

AF:

0.197

AC:

6691

AN:

33901

Ashkenazi Jewish (ASJ)

AF:

0.0190

AC:

359

AN:

18904

East Asian (EAS)

AF:

0.0784

AC:

2313

AN:

29515

South Asian (SAS)

AF:

0.143

AC:

7337

AN:

51183

European-Finnish (FIN)

AF:

0.0692

AC:

2745

AN:

39650

Middle Eastern (MID)

AF:

0.0209

AC:

AN:

3918

European-Non Finnish (NFE)

AF:

0.0182

AC:

14575

AN:

799754

Other (OTH)

AF:

0.0337

AC:

1496

AN:

44340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

1030

2060

3091

4121

5151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

740

1480

2220

2960

3700

<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:

0.0312

AC:

3483

AN:

111716

Hom.:

Cov.:

AF XY:

0.0357

AC XY:

1209

AN XY:

33900

show subpopulations

African (AFR)

AF:

0.00859

AC:

265

AN:

30841

American (AMR)

AF:

0.0941

AC:

984

AN:

10455

Ashkenazi Jewish (ASJ)

AF:

0.0257

AC:

AN:

2651

East Asian (EAS)

AF:

0.0726

AC:

258

AN:

3555

South Asian (SAS)

AF:

0.141

AC:

372

AN:

2638

European-Finnish (FIN)

AF:

0.0734

AC:

439

AN:

5982

Middle Eastern (MID)

AF:

0.0139

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.0196

AC:

1041

AN:

53166

Other (OTH)

AF:

0.0348

AC:

AN:

1523

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

105

210

315

420

525

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:

0.0235

Hom.:

184

Bravo

AF:

0.0350

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.8

(source)

DANN

Benign

0.88

PhyloP100

0.68

PromoterAI

-0.00010

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over