chrX-38286440-TTCCTCCTCTTCCCCCTCCCCTTCC-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBS1BS2

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 (β˜…β˜…).

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

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.385
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]

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ACMG classification

Classification made for transcript

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 GnomAdExome4 at 4 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RPGRNM_001034853.2 linkuse as main transcriptc.2535_2558del p.Glu846_Glu853del inframe_deletion 15/15 ENST00000645032.1 NP_001030025.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RPGRENST00000645032.1 linkuse as main transcriptc.2535_2558del p.Glu846_Glu853del inframe_deletion 15/15 NM_001034853.2 ENSP00000495537 A2Q92834-6

Frequencies

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

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingCenter for Pediatric Genomic Medicine, Children's Mercy Hospital and ClinicsAug 28, 2017- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJan 03, 2017- -
Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 26, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs760332126; hg19: chrX-38145693; API