X-38286437-TCCTTCCTCCTCTTCCCCCTCCCCTTCCTCCTCTTCCCCCTCC-TCCTTCCTCCTCTTCCCCCTCC

Variant names:

• chrX-38286437-TCCTTCCTCCTCTTCCCCCTCC-T
• rs751710678
• NM_001034853.2:c.2541_2561delGGAGGGGGAAGAGGAGGAAGG

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0290
• Publications: 1 publications found

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

ENSG00000250349 (HGNC:):

ACMG classification

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	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: 42 AN: 18068 Hom.: 1 Cov.: 3

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

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

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: 64 AN: 1974

European-Non Finnish (NFE) AF: 0.0143 AC: 9735 AN: 681123

Other (OTH) AF: 0.0357 AC: 1194 AN: 33461

GnomAD4 genome AF: 0.00232 AC: 42 AN: 18080 Hom.: 1 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 1072

African (AFR) AF: 0.00242 AC: 9 AN: 3722

American (AMR) AF: 0.00511 AC: 7 AN: 1371

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 515

East Asian (EAS) AF: 0.00 AC: 0 AN: 612

South Asian (SAS) AF: 0.0172 AC: 3 AN: 174

European-Finnish (FIN) AF: 0.00920 AC: 9 AN: 978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 43

European-Non Finnish (NFE) AF: 0.00136 AC: 14 AN: 10303

Other (OTH) AF: 0.00 AC: 0 AN: 255

Alfa AF: 0.0103 Hom.: 70

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs751710678; hg19: chrX-38145690; COSMIC: COSV58833567;