NM_001034853.2:c.3060_3071dupAGTGGAAGGGGA

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. 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. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 4 publications found

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]

RPGR Gene-Disease associations (from GenCC):

• retinitis pigmentosa 3

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• RPGR-related retinopathy

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• primary ciliary dyskinesia-retinitis pigmentosa syndrome

  Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• macular degeneration, X-linked atrophic

  Inheritance: XL Classification: LIMITED Submitted by: G2P

ENSG00000250349 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001034853.2.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034853.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPGR	NM_001034853.2	MANE Select	c.3060_3071dupAGTGGAAGGGGA	p.Glu1024_Val1025insValGluGlyGlu	disruptive_inframe_insertion	Exon 15 of 15	NP_001030025.1
	RPGR	NM_000328.3		c.1905+1155_1905+1166dupAGTGGAAGGGGA		intron	N/A	NP_000319.1
	RPGR	NM_001367245.1		c.1902+1155_1902+1166dupAGTGGAAGGGGA		intron	N/A	NP_001354174.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPGR	ENST00000645032.1	MANE Select	c.3060_3071dupAGTGGAAGGGGA	p.Glu1024_Val1025insValGluGlyGlu	disruptive_inframe_insertion	Exon 15 of 15	ENSP00000495537.1
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-380184_172-380173dupACTTCCCCTTCC		intron	N/A	ENSP00000417050.1
	RPGR	ENST00000339363.7	TSL:5	c.2520+1155_2520+1166dupAGTGGAAGGGGA		intron	N/A	ENSP00000343671.3

Frequencies

GnomAD3 genomes Cov.: 11

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 11

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.033

Splicing

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

Other links and lift over

dbSNP: rs199896738; hg19: chrX-38145180;