Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001034853.2(RPGR):c.1240G>C (p.Glu414Gln)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10385514

454510 (ClinVar)

Gene: RPGR

Condition: RPGR-related retinopathy

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 4e6dd244-3dcd-473d-bb7f-0471fef55947

Approved on: 2025-05-20

Published on: 2025-05-20

HGVS expressions

NM_001034853.2:c.1240G>C

NM_001034853.2(RPGR):c.1240G>C (p.Glu414Gln)

NC_000023.11:g.38298961C>G

CM000685.2:g.38298961C>G

NC_000023.10:g.38158214C>G

CM000685.1:g.38158214C>G

NC_000023.9:g.38043158C>G

NG_009553.1:g.33575G>C

ENST00000494707.6:c.444G>C

ENST00000642170.1:n.1494G>C

ENST00000642395.2:c.1240G>C

ENST00000642739.1:c.1240G>C

ENST00000644238.1:c.1060-1509G>C

ENST00000644337.1:c.1060-1509G>C

ENST00000645032.1:c.1240G>C

ENST00000645124.1:c.1240G>C

ENST00000646020.1:c.1300G>C

ENST00000318842.11:c.1240G>C

ENST00000339363.7:c.1240G>C

ENST00000378505.6:c.1240G>C

ENST00000464437.1:c.306G>C

ENST00000465127.1:c.172-367160C>G

ENST00000474584.5:c.1240G>C

ENST00000482855.5:c.1240G>C

ENST00000494841.1:n.503G>C

NM_000328.2:c.1240G>C

NM_001034853.1:c.1240G>C

NM_001367245.1:c.1237G>C

NM_001367246.1:c.1060-1509G>C

NM_001367247.1:c.1240G>C

NM_001367248.1:c.1270G>C

NM_001367249.1:c.1237G>C

NM_001367250.1:c.1237G>C

NM_001367251.1:c.1060-1509G>C

NR_159803.1:n.1442G>C

NR_159804.1:n.1291G>C

NR_159805.1:n.1382G>C

NR_159806.1:n.1382G>C

NR_159807.1:n.1382G>C

NR_159808.1:n.1494G>C

NM_000328.3:c.1240G>C

Benign

BP4 BA1

Evidence Links 0

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

X-linked Inherited Retinal Disease VCEP

NM_001034853.2(RPGR):c.1240G>C is a missense variant predicted to cause the substitution of glutamate by glutamine at amino acid 414. This variant is present in gnomAD v.4.1.0 at a frequency of 0.00008303 among hemizygous individuals, with 33 variant alleles / 397,426 total 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 0.119, which is below the ClinGen X-linked IRD VCEP threshold of < 0.183 and predicts a non-damaging effect on the RPGR function. Additionally, the splicing impact predictor SpliceAI gives a delta score of 0.02, which is below the ClinGen X-linked IRD VCEP recommended threshold of <0.1 and does not strongly predict an impact on splicing (BP4_moderate). In summary, this variant is classified as benign for RPGR-related retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen X-linked IRD VCEP: BA1, and BP4_moderate. (VCEP specifications version 1.0.0; date of approval 05/16/2025).

BP4

The computational predictor REVEL gives a score of 0.119, which is below the ClinGen X-linked IRD VCEP threshold of < 0.183 and predicts a non-damaging effect on RPGR function. Additionally, the splicing impact predictor SpliceAI gives a delta score of 0.02, which is below the ClinGen X-linked IRD VCEP recommended threshold of <0.1 and does not strongly predict an impact on splicing (BP4_moderate).

BA1

This variant is present in gnomAD v.4.1.0 at a frequency of 0.00008303 among hemizygous individuals, with 33 variant alleles / 397,426 total alleles, which is higher than the ClinGen X-linked IRD VCEP BA1 threshold of >0.00005 (BA1).

Curation History

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