Variant rs200955614 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 3P and 16B. PM1PM4_SupportingBP6_Very_StrongBA1

The NM_001034853.2(RPGR):c.3051_3053del(p.Glu1018del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 763,134 control chromosomes in the GnomAD database, including 31 homozygotes. There are 381 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 13 hom., 59 hem., cov: 12)

Exomes 𝑓: 0.0018 ( 18 hom. 322 hem. )

Consequence

RPGR
NM_001034853.2 inframe_deletion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 1.16

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]

RPGR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PM1

In a lipid_moiety_binding_region S-geranylgeranyl cysteine (size 0) in uniprot entity RPGR_HUMAN

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-38285945-TTCC-T is Benign according to our data. Variant chrX-38285945-TTCC-T is described in ClinVar as [Likely_benign]. Clinvar id is 445344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPGR	NM_001034853.2 linkuse as main transcript	c.3051_3053del	p.Glu1018del	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 linkuse as main transcript	c.3051_3053del	p.Glu1018del	inframe_deletion	15/15		NM_001034853.2	ENSP00000495537	A2	Q92834-6

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

679

AN:

63038

Hom.:

Cov.:

AF XY:

0.00593

AC XY:

AN XY:

9946

show subpopulations

Gnomad AFR

AF:

0.0393

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00726

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:

0.000145

Gnomad OTH

AF:

0.00893

GnomAD3 exomes

AF:

0.00409

AC:

436

AN:

106544

Hom.:

AF XY:

0.00339

AC XY:

106

AN XY:

31290

show subpopulations

Gnomad AFR exome

AF:

0.0432

Gnomad AMR exome

AF:

0.00326

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000113

Gnomad SAS exome

AF:

0.000241

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.00252

GnomAD4 exome

AF:

0.00177

AC:

1241

AN:

700068

Hom.:

AF XY:

0.00157

AC XY:

322

AN XY:

204460

show subpopulations

Gnomad4 AFR exome

AF:

0.0551

Gnomad4 AMR exome

AF:

0.00420

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000240

Gnomad4 SAS exome

AF:

0.000161

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000548

Gnomad4 OTH exome

AF:

0.00492

GnomAD4 genome

AF:

0.0108

AC:

679

AN:

63066

Hom.:

Cov.:

AF XY:

0.00592

AC XY:

AN XY:

9962

show subpopulations

Gnomad4 AFR

AF:

0.0393

Gnomad4 AMR

AF:

0.00724

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000145

Gnomad4 OTH

AF:

0.00883

Alfa

AF:

0.00619

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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 10, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 05, 2019	- -

Primary ciliary dyskinesia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over