X-38269772-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000328.3(RPGR):c.2302C>A(p.Pro768Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00475 in 1,207,676 control chromosomes in the GnomAD database, including 192 homozygotes. There are 1,489 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 91 hom., 704 hem., cov: 23)

Exomes 𝑓: 0.0027 ( 101 hom. 785 hem. )

Consequence

RPGR
NM_000328.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 4.87

Variant links:

Genes affected

ENSG00000250349 (HGNC:):

ENSG00000250349 links:

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018976331).

BP6

Variant X-38269772-G-T is Benign according to our data. Variant chrX-38269772-G-T is described in ClinVar as [Benign]. Clinvar id is 255835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
RPGR	NM_000328.3 link	c.2302C>A	p.Pro768Thr	missense_variant	Exon 19 of 19	NP_000319.1	Q92834-2
RPGR	NM_001367245.1 link	c.2299C>A	p.Pro767Thr	missense_variant	Exon 19 of 19	NP_001354174.1
RPGR	NM_001367246.1 link	c.2116C>A	p.Pro706Thr	missense_variant	Exon 18 of 18	NP_001354175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000250349	ENST00000465127.1 link	c.172-396349G>T		intron_variant	Intron 3 of 8	5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

AF:

0.0249

AC:

2766

AN:

111229

Hom.:

Cov.:

AF XY:

0.0210

AC XY:

704

AN XY:

33461

show subpopulations

Gnomad AFR

AF:

0.0856

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0116

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000375

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000283

Gnomad OTH

AF:

0.0140

GnomAD3 exomes

AF:

0.00726

AC:

1325

AN:

182556

Hom.:

AF XY:

0.00413

AC XY:

278

AN XY:

67278

show subpopulations

Gnomad AFR exome

AF:

0.0889

Gnomad AMR exome

AF:

0.00468

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000158

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000221

Gnomad OTH exome

AF:

0.00378

GnomAD4 exome

AF:

0.00271

AC:

2973

AN:

1096396

Hom.:

101

Cov.:

AF XY:

0.00217

AC XY:

785

AN XY:

361928

show subpopulations

Gnomad4 AFR exome

AF:

0.0913

Gnomad4 AMR exome

AF:

0.00557

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000166

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000112

Gnomad4 OTH exome

AF:

0.00547

GnomAD4 genome

AF:

0.0248

AC:

2765

AN:

111280

Hom.:

Cov.:

AF XY:

0.0210

AC XY:

704

AN XY:

33522

show subpopulations

Gnomad4 AFR

AF:

0.0854

Gnomad4 AMR

AF:

0.0116

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000376

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000283

Gnomad4 OTH

AF:

0.0139

Alfa

AF:

0.00370

Hom.:

114

Bravo

AF:

0.0297

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0890

AC:

341

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00832

AC:

1010

EpiCase

AF:

0.000382

EpiControl

AF:

0.000832

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 28, 2014

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:2

Jul 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.092

.;.;T;.;.

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.76

.;T;T;T;T

MetaRNN

Benign

0.0019

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

.;.;L;.;.

PROVEAN

Uncertain

-2.9

D;.;N;.;.

REVEL

Benign

0.071

Sift

Benign

0.19

T;.;T;.;.

Sift4G

Benign

0.063

T;.;T;.;.

Polyphen

0.85

P;P;.;.;.

Vest4

0.19

MVP

0.19

ClinPred

0.044

GERP RS

3.3

Varity_R

0.075

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