X-38285927-CTCCCCTTCCACT-CTCCCCTTCCACTTCCCCTTCCACT

Variant names:

• chrX-38285927-C-CTCCCCTTCCACT
• rs199896738
• NM_001034853.2:c.3060_3071dupAGTGGAAGGGGA

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001034853.2(RPGR):​c.3060_3071dupAGTGGAAGGGGA​(p.Glu1024_Val1025insValGluGlyGlu) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 11)
• Consequence: RPGR NM_001034853.2 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

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]

ENSG00000250349 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001034853.2.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGR	NM_001034853.2	c.3060_3071dupAGTGGAAGGGGA	p.Glu1024_Val1025insValGluGlyGlu	disruptive_inframe_insertion	Exon 15 of 15	ENST00000645032.1	NP_001030025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPGR	ENST00000645032.1	c.3060_3071dupAGTGGAAGGGGA	p.Glu1024_Val1025insValGluGlyGlu	disruptive_inframe_insertion	Exon 15 of 15		NM_001034853.2	ENSP00000495537.1
ENSG00000250349	ENST00000465127.1	c.172-380184_172-380173dupACTTCCCCTTCC		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

Frequencies

GnomAD3 genomes Cov.: 11

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 11

ClinVar

Not reported in ClinVar

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: rs199896738; hg19: chrX-38145180;