X-38286329-TTCC-T

Position:

• chrX-38286329-TTCC-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_Supporting BP6_Very_Strong BA1

The NM_001034853.2(RPGR):​c.2667_2669delGGA​(p.Glu890del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.047 in 598,218 control chromosomes in the GnomAD database, including 1,918 homozygotes. There are 6,699 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.090 (61 hom., 12 hem., cov: 2)
  • Exomes 𝑓: 0.046 (1857 hom. 6687 hem.)
• Consequence: RPGR NM_001034853.2 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0900

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]

ENSG00000250349 (HGNC:):

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-38286329-TTCC-T is Benign according to our data. Variant chrX-38286329-TTCC-T is described in ClinVar as [Likely_benign]. Clinvar id is 257196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38286329-TTCC-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPGR	NM_001034853.2	c.2667_2669delGGA	p.Glu890del	disruptive_inframe_deletion	15/15	ENST00000645032.1	NP_001030025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPGR	ENST00000645032.1	c.2667_2669delGGA	p.Glu890del	disruptive_inframe_deletion	15/15		NM_001034853.2	ENSP00000495537.1
ENSG00000250349	ENST00000465127.1	c.172-379789_172-379787delCTC		intron_variant		5		ENSP00000417050.1

Frequencies

GnomAD3 genomes AF: 0.0900 AC: 798 AN: 8868 Hom.: 61 Cov.: 2 AF XY: 0.0335 AC XY: 12 AN XY: 358

Gnomad AFR AF: 0.0633

Gnomad AMI AF: 0.0698

Gnomad AMR AF: 0.0564

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.0707

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.130

GnomAD3 exomes AF: 0.0144 AC: 611 AN: 42549 Hom.: 44 AF XY: 0.00601 AC XY: 60 AN XY: 9977

Gnomad AFR exome AF: 0.0237

Gnomad AMR exome AF: 0.0107

Gnomad ASJ exome AF: 0.0171

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00546

Gnomad FIN exome AF: 0.000852

Gnomad NFE exome AF: 0.0246

Gnomad OTH exome AF: 0.0268

GnomAD4 exome AF: 0.0463 AC: 27313 AN: 589351 Hom.: 1857 AF XY: 0.0467 AC XY: 6687 AN XY: 143085

Gnomad4 AFR exome AF: 0.0317

Gnomad4 AMR exome AF: 0.0379

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.000392

Gnomad4 SAS exome AF: 0.0151

Gnomad4 FIN exome AF: 0.193

Gnomad4 NFE exome AF: 0.0432

Gnomad4 OTH exome AF: 0.0766

GnomAD4 genome AF: 0.0900 AC: 798 AN: 8867 Hom.: 61 Cov.: 2 AF XY: 0.0334 AC XY: 12 AN XY: 359

Gnomad4 AFR AF: 0.0633

Gnomad4 AMR AF: 0.0566

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0169

Gnomad4 FIN AF: 0.0707

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.128

Alfa AF: 0.00562 Hom.: 36

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Jan 29, 2016	- -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 12, 2019

- -

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: rs199663434; hg19: chrX-38145582;