rs281865313

Variant names:

• chrX-38269698-GTGGTTCTGGTCGGCATCTT-G
• rs281865313
• ENST00000465127.1:c.172-396421_172-396403delGGTTCTGGTCGGCATCTTT

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_000328.3(RPGR):​c.2357_2375delAAGATGCCGACCAGAACCA​(p.Lys786ThrfsTer2) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 22)
• Consequence: RPGR NM_000328.3 frameshift
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 3.84

Genes affected

ENSG00000250349 (HGNC:):

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 Uncertain_significance. Variant got 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0372 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGR	NM_000328.3	c.2357_2375delAAGATGCCGACCAGAACCA	p.Lys786ThrfsTer2	frameshift_variant	Exon 19 of 19		NP_000319.1
RPGR	NM_001367245.1	c.2354_2372delAAGATGCCGACCAGAACCA	p.Lys785ThrfsTer2	frameshift_variant	Exon 19 of 19		NP_001354174.1
RPGR	NM_001367246.1	c.2171_2189delAAGATGCCGACCAGAACCA	p.Lys724ThrfsTer2	frameshift_variant	Exon 18 of 18		NP_001354175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000250349	ENST00000465127.1	c.172-396421_172-396403delGGTTCTGGTCGGCATCTTT		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

Frequencies

GnomAD3 genomes Cov.: 22

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 22

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

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Retina International

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

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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: rs281865313; hg19: chrX-38128951;