rs760332126

chrX-38286440-TTCCTCCTCTTCCCCCTCCCCTTCC-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BS1 BS2

The NM_001034853.2(RPGR):c.2535_2558del(p.Glu846_Glu853del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000289 in 689,456 control chromosomes in the GnomAD database, including 4 homozygotes. There are 52 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., 0 hem., cov: 3)
  • Exomes 𝑓: 0.00027 (4 hom. 52 hem.)
• Consequence: RPGR NM_001034853.2 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.385

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 -14 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001034853.2.
• BP6: Variant X-38286440-TTCCTCCTCTTCCCCCTCCCCTTCC-T is Benign according to our data. Variant chrX-38286440-TTCCTCCTCTTCCCCCTCCCCTTCC-T is described in ClinVar as [Likely_benign]. Clinvar id is 445999.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 = 0.00107 (15/14044) while in subpopulation AFR AF= 0.00548 (14/2554). AF 95% confidence interval is 0.00331. There are 0 homozygotes in gnomad4. There are 0 alleles in male gnomad4 subpopulation. Median coverage is 3. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPGR	NM_001034853.2	c.2535_2558del	p.Glu846_Glu853del	inframe_deletion	15/15	ENST00000645032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPGR	ENST00000645032.1	c.2535_2558del	p.Glu846_Glu853del	inframe_deletion	15/15		NM_001034853.2	A2

Frequencies

GnomAD3 genomes AF: 0.00107 AC: 15 AN: 14027 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 843

Gnomad AFR AF: 0.00549

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000894

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: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000645 AC: 33 AN: 51199 Hom.: 3 AF XY: 0.000111 AC XY: 1 AN XY: 9013

Gnomad AFR exome AF: 0.00670

Gnomad AMR exome AF: 0.000700

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000211

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000272 AC: 184 AN: 675412 Hom.: 4 AF XY: 0.000279 AC XY: 52 AN XY: 186466

Gnomad4 AFR exome AF: 0.0101

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000384

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000230

Gnomad4 OTH exome AF: 0.000672

GnomAD4 genome AF: 0.00107 AC: 15 AN: 14044 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 846

Gnomad4 AFR AF: 0.00548

Gnomad4 AMR AF: 0.000890

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00506 Hom.: 15

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 28, 2017	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Jan 03, 2017	- -

Primary ciliary dyskinesia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs760332126; hg19: chrX-38145693;