X-38286437-TCCTTCCTCCTCTTCCCCCTCC-T

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.2541_2561delGGAGGGGGAAGAGGAGGAAGG(p.Glu848_Gly854del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 855,600 control chromosomes in the GnomAD database, including 589 homozygotes. There are 6,664 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 (★★). Synonymous variant affecting the same amino acid position (i.e. G847G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., 0 hem., cov: 3)

Exomes 𝑓: 0.025 ( 588 hom. 6664 hem. )

Consequence

RPGR
NM_001034853.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0290

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 -14 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001034853.2.

BP6

Variant X-38286437-TCCTTCCTCCTCTTCCCCCTCC-T is Benign according to our data. Variant chrX-38286437-TCCTTCCTCCTCTTCCCCCTCC-T is described in ClinVar as Benign. ClinVar VariationId is 237685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0852 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.2541_2561delGGAGGGGGAAGAGGAGGAAGG	p.Glu848_Gly854del	disruptive_inframe_deletion	Exon 15 of 15	NP_001030025.1
RPGR	NM_000328.3		c.1905+636_1905+656delGGAGGGGGAAGAGGAGGAAGG		intron	N/A	NP_000319.1
RPGR	NM_001367245.1		c.1902+636_1902+656delGGAGGGGGAAGAGGAGGAAGG		intron	N/A	NP_001354174.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RPGR	ENST00000645032.1	MANE Select	c.2541_2561delGGAGGGGGAAGAGGAGGAAGG	p.Glu848_Gly854del	disruptive_inframe_deletion	Exon 15 of 15	ENSP00000495537.1
ENSG00000250349	ENST00000465127.1	TSL:5	c.172-379642_172-379622delCCCTTCCTCCTCTTCCCCCTC		intron	N/A	ENSP00000417050.1
RPGR	ENST00000339363.7	TSL:5	c.2520+636_2520+656delGGAGGGGGAAGAGGAGGAAGG		intron	N/A	ENSP00000343671.3

Frequencies

GnomAD3 genomes

AF:

0.00232

AC:

AN:

18068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00510

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0172

Gnomad FIN

AF:

0.00920

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00136

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0224

AC:

1123

AN:

50113

AF XY:

0.0154

show subpopulations

Gnomad AFR exome

AF:

0.0292

Gnomad AMR exome

AF:

0.0314

Gnomad ASJ exome

AF:

0.00187

Gnomad EAS exome

AF:

0.0200

Gnomad FIN exome

AF:

0.0444

Gnomad NFE exome

AF:

0.00751

Gnomad OTH exome

AF:

0.0120

GnomAD4 exome

AF:

0.0246

AC:

20632

AN:

837520

Hom.:

588

AF XY:

0.0282

AC XY:

6664

AN XY:

236558

show subpopulations

African (AFR)

AF:

0.0689

AC:

1258

AN:

18265

American (AMR)

AF:

0.0891

AC:

1397

AN:

15674

Ashkenazi Jewish (ASJ)

AF:

0.0403

AC:

457

AN:

11354

East Asian (EAS)

AF:

0.0878

AC:

1580

AN:

17986

South Asian (SAS)

AF:

0.0849

AC:

2746

AN:

32353

European-Finnish (FIN)

AF:

0.0869

AC:

2201

AN:

25330

Middle Eastern (MID)

AF:

0.0324

AC:

AN:

1974

European-Non Finnish (NFE)

AF:

0.0143

AC:

9735

AN:

681123

Other (OTH)

AF:

0.0357

AC:

1194

AN:

33461

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

572

1143

1715

2286

2858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

226

452

678

904

1130

<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:

0.00232

AC:

AN:

18080

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

1072

show subpopulations

African (AFR)

AF:

0.00242

AC:

AN:

3722

American (AMR)

AF:

0.00511

AC:

AN:

1371

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

515

East Asian (EAS)

AF:

0.00

AC:

AN:

612

South Asian (SAS)

AF:

0.0172

AC:

AN:

174

European-Finnish (FIN)

AF:

0.00920

AC:

AN:

978

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00136

AC:

AN:

10303

Other (OTH)

AF:

0.00

AC:

AN:

255

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0103

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

not provided

Benign:1

Aug 31, 2016

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.029

Mutation Taster

=199/1

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over