rs199663434

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBA1

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

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0900
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
RPGRNM_001034853.2 linkuse as main transcriptc.2667_2669delGGA p.Glu890del disruptive_inframe_deletion 15/15 ENST00000645032.1 NP_001030025.1 Q92834-6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RPGRENST00000645032.1 linkuse as main transcriptc.2667_2669delGGA p.Glu890del disruptive_inframe_deletion 15/15 NM_001034853.2 ENSP00000495537.1 Q92834-6
ENSG00000250349ENST00000465127.1 linkuse as main transcriptc.172-379789_172-379787delCTC intron_variant 5 ENSP00000417050.1 B4E171

Frequencies

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

Submissions by phenotype

not specified Benign:2
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 28, 2016Variant 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 submitterclinical testingPreventionGenetics, part of Exact SciencesJan 29, 2016- -
Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxAug 12, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs199663434; hg19: chrX-38145582; API