rs201242851

chrX-38323400-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001034853.2(RPGR):c.153C>T(p.Thr51=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000412 in 1,201,767 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 151 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., 6 hem., cov: 23)
  • Exomes 𝑓: 0.00042 (0 hom. 145 hem.)
• Consequence: RPGR NM_001034853.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.0003513
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.59

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant X-38323400-G-A is Benign according to our data. Variant chrX-38323400-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 414014.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38323400-G-A is described in Lovd as [Likely_benign]. Variant chrX-38323400-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=2.59 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPGR	NM_001034853.2	c.153C>T	p.Thr51=	splice_region_variant, synonymous_variant	2/15	ENST00000645032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPGR	ENST00000645032.1	c.153C>T	p.Thr51=	splice_region_variant, synonymous_variant	2/15		NM_001034853.2	A2

Frequencies

GnomAD3 genomes AF: 0.000305 AC: 34 AN: 111645 Hom.: 0 Cov.: 23 AF XY: 0.000177 AC XY: 6 AN XY: 33873

Gnomad AFR AF: 0.0000326

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000621

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000385 AC: 68 AN: 176706 Hom.: 0 AF XY: 0.000388 AC XY: 24 AN XY: 61782

Gnomad AFR exome AF: 0.0000779

Gnomad AMR exome AF: 0.0000370

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000849

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000423 AC: 461 AN: 1090122 Hom.: 0 Cov.: 27 AF XY: 0.000407 AC XY: 145 AN XY: 356190

Gnomad4 AFR exome AF: 0.000114

Gnomad4 AMR exome AF: 0.0000571

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000247

Gnomad4 NFE exome AF: 0.000528

Gnomad4 OTH exome AF: 0.000306

GnomAD4 genome AF: 0.000305 AC: 34 AN: 111645 Hom.: 0 Cov.: 23 AF XY: 0.000177 AC XY: 6 AN XY: 33873

Gnomad4 AFR AF: 0.0000326

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000621

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000515 Hom.: 23

Bravo AF: 0.000397

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

RPGR-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 04, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

RPGR: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	4.9
Dann	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00035
dbscSNV1_RF	Benign	0.054
SpliceAI score (max)		0.010		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: rs201242851; hg19: chrX-38182653; COSMIC: COSV58832561; COSMIC: COSV58832561;