X-38269557-CATAAGTT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000339363.7(RPGR):c.*62_*68del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00797 in 814,350 control chromosomes in the GnomAD database, including 257 homozygotes. There are 1,592 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (143 hom., 895 hem., cov: 21)
  • Exomes 𝑓: 0.0042 (114 hom. 697 hem.)
• Consequence: RPGR ENST00000339363.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.99

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 -10 ACMG points.

• BP6: Variant X-38269557-CATAAGTT-C is Benign according to our data. Variant chrX-38269557-CATAAGTT-C is described in ClinVar as [Benign]. Clinvar id is 1282240.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPGR	NM_000328.3	c.*62_*68del		3_prime_UTR_variant	19/19
RPGR	NM_001367245.1	c.*62_*68del		3_prime_UTR_variant	19/19
RPGR	NM_001367246.1	c.*62_*68del		3_prime_UTR_variant	18/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPGR	ENST00000339363.7	c.*62_*68del		3_prime_UTR_variant	18/18	5		P4
RPGR	ENST00000642395.2	c.*62_*68del		3_prime_UTR_variant	19/19			A2
RPGR	ENST00000644238.1	c.*62_*68del		3_prime_UTR_variant	16/16

Frequencies

GnomAD3 genomes AF: 0.0314 AC: 3506 AN: 111551 Hom.: 143 Cov.: 21 AF XY: 0.0265 AC XY: 894 AN XY: 33769

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00917

Gnomad SAS AF: 0.00111

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0193

GnomAD4 exome AF: 0.00425 AC: 2984 AN: 702747 Hom.: 114 AF XY: 0.00359 AC XY: 697 AN XY: 194205

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.00643

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00969

Gnomad4 SAS exome AF: 0.000435

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000164

Gnomad4 OTH exome AF: 0.00769

GnomAD4 genome AF: 0.0314 AC: 3508 AN: 111603 Hom.: 143 Cov.: 21 AF XY: 0.0265 AC XY: 895 AN XY: 33831

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0125

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00920

Gnomad4 SAS AF: 0.00112

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0191

Alfa AF: 0.0244 Hom.: 77

Bravo AF: 0.0380

Asia WGS AF: 0.00880 AC: 22 AN: 2510

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 14, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11279874; hg19: chrX-38128810;