Variant: NM_001034853.2(RPGR):c.223A>G (p.Ile75Val)

CA202241

100560 (ClinVar)

Gene: RPGR

Condition: RPGR-related retinopathy

Inheritance Mode: X-linked inheritance

UUID: 8f0af1cf-531d-4f65-8c6c-53d52b28ff28

Approved on: 2025-08-04

Published on: 2025-08-04

HGVS expressions

NM_001034853.2:c.223A>G
NM_001034853.2(RPGR):c.223A>G (p.Ile75Val)
NC_000023.11:g.38322877T>C
CM000685.2:g.38322877T>C
NC_000023.10:g.38182130T>C
CM000685.1:g.38182130T>C
NC_000023.9:g.38067074T>C
NG_009553.1:g.9659A>G
ENST00000642170.1:n.633A>G
ENST00000642373.1:c.223A>G
ENST00000642395.2:c.223A>G
ENST00000642558.1:c.154+522A>G
ENST00000642739.1:c.223A>G
ENST00000644238.1:c.223A>G
ENST00000644337.1:c.223A>G
ENST00000645032.1:c.223A>G
ENST00000645124.1:c.223A>G
ENST00000646020.1:c.223A>G
ENST00000647261.1:c.223A>G
ENST00000318842.11:c.223A>G
ENST00000339363.7:c.223A>G
ENST00000378505.6:c.223A>G
ENST00000465127.1:c.172-343244T>C
ENST00000474584.5:c.223A>G
ENST00000482855.5:c.223A>G
NM_000328.2:c.223A>G
NM_001034853.1:c.223A>G
NM_001367245.1:c.223A>G
NM_001367246.1:c.223A>G
NM_001367247.1:c.223A>G
NM_001367248.1:c.253A>G
NM_001367249.1:c.223A>G
NM_001367250.1:c.223A>G
NM_001367251.1:c.223A>G
NR_159803.1:n.365A>G
NR_159804.1:n.365A>G
NR_159805.1:n.365A>G
NR_159806.1:n.365A>G
NR_159807.1:n.365A>G
NR_159808.1:n.633A>G
NM_000328.3:c.223A>G

Benign

• Met criteria codes: BA1

• Not Met criteria codes: BP4 PP3

Expert Panel

X-linked Inherited Retinal Disease VCEP

Criteria Specification Information

Criteria Specification: ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RPGR Version 1.0.0

Evidence submitted by expert panel

X-linked Inherited Retinal Disease VCEP

NM_001034853.2(RPGR):c.223A>G (p.Ile75Val) is a missense variant predicted to cause substitution of isoleucine by valine at amino acid 75. This variant is present in gnomAD v.4.1.0 at a frequency of 0.01338 among hemizygous individuals, with 5304 variant alleles / 396,459 total hemizygous alleles, which is higher than the ClinGen X-linked IRD VCEP BA1 threshold of >0.000005 (BA1). The computational predictor REVEL gives a score of 0.218, which is below the ClinGen X-linked IRD VCEP threshold of <0.290 and predicts a non-damaging effect on RPGR function. However, the splicing impact predictor SpliceAI gives a delta score of 0.12 for acceptor gain, which falls in the intermediate range above the ClinGen X-linked IRD VCEP recommended BP4 threshold of <0.1 but lower than the PP3 threshold of >0.2, so neither in silico code is met. In summary, this variant is classified as benign for RPGR-related retinopathy based on the ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RPGR Version 1.0.0; BA1. (date of approval 05/16/2025).

Met criteria codes

• BA1: This variant is present in gnomAD v.4.1.0 at a frequency of 0.01338 among hemizygous individuals, with 5304 variant alleles / 396,459 total hemizygous alleles, which is higher than the ClinGen X-linked IRD VCEP BA1 threshold of >0.000005 (BA1).

Not Met criteria codes

• BP4: The computational predictor REVEL gives a score of 0.218, which is below the ClinGen X-linked IRD VCEP threshold of <0.290 and predicts a non-damaging effect on RPGR function. However, the splicing impact predictor SpliceAI gives a delta score of 0.12 for acceptor gain, which falls in the intermediate range above the ClinGen X-linked IRD VCEP recommended BP4 threshold of <0.1 but lower than the PP3 threshold of >0.2, so neither in silico code is met.
• PP3: The computational predictor REVEL gives a score of 0.218, which is below the ClinGen X-linked IRD VCEP threshold of <0.290 and predicts a non-damaging effect on RPGR function. However, the splicing impact predictor SpliceAI gives a delta score of 0.12 for acceptor gain, which falls in the intermediate range above the ClinGen X-linked IRD VCEP recommended BP4 threshold of <0.1 but lower than the PP3 threshold of >0.2, so neither in silico code is met.