chrX-38285945-TTCC-T

Variant names:

• chrX-38285945-TTCC-T
• rs200955614
• NM_001034853.2:c.3051_3053delGGA

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_Supporting BP6_Very_Strong BA1

The NM_001034853.2(RPGR):​c.3051_3053delGGA​(p.Glu1018del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 763,134 control chromosomes in the GnomAD database, including 31 homozygotes. There are 381 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (13 hom., 59 hem., cov: 12)
  • Exomes 𝑓: 0.0018 (18 hom. 322 hem.)
• Consequence: RPGR NM_001034853.2 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.16
• 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 -15 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001034853.2. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant X-38285945-TTCC-T is Benign according to our data. Variant chrX-38285945-TTCC-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0523 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.3051_3053delGGA	p.Glu1018del	disruptive_inframe_deletion	Exon 15 of 15	NP_001030025.1
	RPGR	NM_000328.3		c.1905+1146_1905+1148delGGA		intron	N/A	NP_000319.1
	RPGR	NM_001367245.1		c.1902+1146_1902+1148delGGA		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.3051_3053delGGA	p.Glu1018del	disruptive_inframe_deletion	Exon 15 of 15	ENSP00000495537.1
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-380173_172-380171delCTC		intron	N/A	ENSP00000417050.1
	RPGR	ENST00000339363.7	TSL:5	c.2520+1146_2520+1148delGGA		intron	N/A	ENSP00000343671.3

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 679 AN: 63038 Hom.: 13 Cov.: 12

Gnomad AFR AF: 0.0393

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00726

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000145

Gnomad OTH AF: 0.00893

GnomAD2 exomes AF: 0.00409 AC: 436 AN: 106544 AF XY: 0.00339

Gnomad AFR exome AF: 0.0432

Gnomad AMR exome AF: 0.00326

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000113

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.00252

GnomAD4 exome AF: 0.00177 AC: 1241 AN: 700068 Hom.: 18 AF XY: 0.00157 AC XY: 322 AN XY: 204460

African (AFR) AF: 0.0551 AC: 970 AN: 17589

American (AMR) AF: 0.00420 AC: 95 AN: 22599

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11154

East Asian (EAS) AF: 0.000240 AC: 3 AN: 12521

South Asian (SAS) AF: 0.000161 AC: 7 AN: 43590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15682

Middle Eastern (MID) AF: 0.000430 AC: 1 AN: 2327

European-Non Finnish (NFE) AF: 0.0000548 AC: 30 AN: 547149

Other (OTH) AF: 0.00492 AC: 135 AN: 27457

GnomAD4 genome AF: 0.0108 AC: 679 AN: 63066 Hom.: 13 Cov.: 12 AF XY: 0.00592 AC XY: 59 AN XY: 9962

African (AFR) AF: 0.0393 AC: 633 AN: 16111

American (AMR) AF: 0.00724 AC: 34 AN: 4696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1740

East Asian (EAS) AF: 0.00 AC: 0 AN: 1641

South Asian (SAS) AF: 0.00 AC: 0 AN: 674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 110

European-Non Finnish (NFE) AF: 0.000145 AC: 5 AN: 34529

Other (OTH) AF: 0.00883 AC: 7 AN: 793

Alfa AF: 0.00619 Hom.: 28

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Jan 10, 2018

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Aug 28, 2017

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Oct 05, 2019

GeneDx

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=83/17	polymorphism (auto)

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

Other links and lift over

dbSNP: rs200955614; hg19: chrX-38145198;