Variant: NM_001034853.2(RPGR):c.1296A>T (p.Glu432Asp)

CA10385495

255832 (ClinVar)

Gene: RPGR

Condition: RPGR-related retinopathy

Inheritance Mode: X-linked inheritance

UUID: 25a2ffd7-83e5-4913-bb85-f02dbc76afbc

Approved on: 2025-08-01

Published on: 2025-08-02

HGVS expressions

NM_001034853.2:c.1296A>T
NM_001034853.2(RPGR):c.1296A>T (p.Glu432Asp)
NC_000023.11:g.38297402T>A
CM000685.2:g.38297402T>A
NC_000023.10:g.38156655T>A
CM000685.1:g.38156655T>A
NC_000023.9:g.38041599T>A
NG_009553.1:g.35134A>T
ENST00000494707.6:c.500A>T
ENST00000642170.1:n.1550A>T
ENST00000642395.2:c.1296A>T
ENST00000642739.1:c.1296A>T
ENST00000644238.1:c.1110A>T
ENST00000644337.1:c.1110A>T
ENST00000645032.1:c.1296A>T
ENST00000645124.1:c.1296A>T
ENST00000646020.1:c.1356A>T
ENST00000318842.11:c.1296A>T
ENST00000339363.7:c.1296A>T
ENST00000378505.6:c.1296A>T
ENST00000465127.1:c.172-368719T>A
ENST00000474584.5:c.1296A>T
ENST00000482855.5:c.1296A>T
ENST00000494841.1:n.559A>T
NM_000328.2:c.1296A>T
NM_001034853.1:c.1296A>T
NM_001367245.1:c.1293A>T
NM_001367246.1:c.1110A>T
NM_001367247.1:c.1296A>T
NM_001367248.1:c.1326A>T
NM_001367249.1:c.1293A>T
NM_001367250.1:c.1293A>T
NM_001367251.1:c.1110A>T
NR_159803.1:n.1498A>T
NR_159804.1:n.1372A>T
NR_159805.1:n.1438A>T
NR_159806.1:n.1438A>T
NR_159807.1:n.1438A>T
NR_159808.1:n.1550A>T
NM_000328.3:c.1296A>T

Benign

• Met criteria codes: BP4_Strong BA1

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.1296A>T (p.Glu432Asp) is a missense variant predicted to cause substitution of glutamic acid by aspartic acid at amino acid 432. This variant is present in gnomAD v4.1.0 at a frequency of 0.0009778 among hemizygous individuals, with 385 variant alleles / 393,794 total hemizygous alleles, which is higher than the ClinGen X-linked IRD VCEP BA1 threshold of >0.00005 (BA1). The computational predictor REVEL gives a score of 0.009, which is below the ClinGen X-linked IRD VCEP threshold of <0.016 and predicts a non-damaging effect on RPGR function. Additionally, the splicing impact predictor SpliceAI gives a delta score of 0.03, which is below the ClinGen X-linked IRD VCEP recommended threshold of <0.1 and does not strongly predict an impact on splicing (BP4_Strong). 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 and BP4_Strong. (date of approval 05/16/2025).

Met criteria codes

• BP4_Strong: The computational predictor REVEL gives a score of 0.009, which is below the ClinGen X-linked IRD VCEP threshold of < 0.016 and predicts a non-damaging effect on RPGR function. Additionally, the splicing impact predictor SpliceAI gives a delta score of 0.03, which is below the ClinGen X-linked IRD VCEP recommended threshold of <0.1 and does not strongly predict an impact on splicing (BP4_Strong).
• BA1: This variant is present in gnomAD v.4.1.0 at a frequency of 0.0009778 among hemizygous individuals, with 385 variant alleles / 393,794 total hemizygous alleles, which is higher than the ClinGen X-linked IRD VCEP BA1 threshold of >0.00005 (BA1).