rs201730068

chrX-38286662-TTCC-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_Supporting BP6_Very_Strong BS1 BS2

The NM_001034853.2(RPGR):c.2334_2336del(p.Glu779del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,123,100 control chromosomes in the GnomAD database, including 35 homozygotes. There are 446 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (16 hom., 82 hem., cov: 12)
  • Exomes 𝑓: 0.0013 (19 hom. 364 hem.)
• Consequence: RPGR NM_001034853.2 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.518

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]

ACMG classification

Verdict is Benign. Variant got -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-38286662-TTCC-T is Benign according to our data. Variant chrX-38286662-TTCC-T is described in ClinVar as [Likely_benign]. Clinvar id is 446048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.01 (777/77436) while in subpopulation AFR AF= 0.0353 (696/19714). AF 95% confidence interval is 0.0331. There are 16 homozygotes in gnomad4. There are 82 alleles in male gnomad4 subpopulation. Median coverage is 12. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 16 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPGR	NM_001034853.2	c.2334_2336del	p.Glu779del	inframe_deletion	15/15	ENST00000645032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPGR	ENST00000645032.1	c.2334_2336del	p.Glu779del	inframe_deletion	15/15		NM_001034853.2	A2

Frequencies

GnomAD3 genomes AF: 0.0100 AC: 777 AN: 77394 Hom.: 16 Cov.: 12 AF XY: 0.00690 AC XY: 82 AN XY: 11880

Gnomad AFR AF: 0.0354

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00948

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: 0.000124

Gnomad OTH AF: 0.0117

GnomAD3 exomes AF: 0.00398 AC: 451 AN: 113351 Hom.: 8 AF XY: 0.00271 AC XY: 109 AN XY: 40281

Gnomad AFR exome AF: 0.0464

Gnomad AMR exome AF: 0.00512

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000211

Gnomad FIN exome AF: 0.0000850

Gnomad NFE exome AF: 0.0000470

Gnomad OTH exome AF: 0.00275

GnomAD4 exome AF: 0.00132 AC: 1379 AN: 1045664 Hom.: 19 AF XY: 0.00107 AC XY: 364 AN XY: 339624

Gnomad4 AFR exome AF: 0.0406

Gnomad4 AMR exome AF: 0.00575

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000242

Gnomad4 FIN exome AF: 0.0000537

Gnomad4 NFE exome AF: 0.0000601

Gnomad4 OTH exome AF: 0.00356

GnomAD4 genome AF: 0.0100 AC: 777 AN: 77436 Hom.: 16 Cov.: 12 AF XY: 0.00688 AC XY: 82 AN XY: 11918

Gnomad4 AFR AF: 0.0353

Gnomad4 AMR AF: 0.00946

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000124

Gnomad4 OTH AF: 0.0115

Alfa AF: 0.00652 Hom.: 32

Asia WGS AF: 0.00159 AC: 4 AN: 2521

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Jun 06, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 28, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 14, 2018	- -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs201730068; hg19: chrX-38145915;