Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene label mismatch: RPGR vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001034853.2(RPGR):c.3231T>A (p.Asn1077Lys)

CA10385168

403392 (ClinVar)

Gene: RPGR
Condition: RPGR-related retinopathy
Inheritance Mode: X-linked inheritance (dominant (HP:0001423))
Link to MONDO
UUID: ac760acb-3d28-468a-b700-a556a116ea4c
Approved on: 2025-05-20
Published on: 2025-05-21

HGVS expressions

NM_001034853.2:c.3231T>A
NM_001034853.2(RPGR):c.3231T>A (p.Asn1077Lys)
NC_000023.11:g.38285768A>T
CM000685.2:g.38285768A>T
NC_000023.10:g.38145021A>T
CM000685.1:g.38145021A>T
NC_000023.9:g.38029965A>T
NG_009553.1:g.46768T>A
ENST00000494707.6:c.953+2097T>A
ENST00000642170.1:n.1826+5191T>A
ENST00000642395.2:c.1905+1326T>A
ENST00000642739.1:c.1572+5191T>A
ENST00000644238.1:c.1386+5191T>A
ENST00000644337.1:c.1719+1326T>A
ENST00000645032.1:c.3231T>A
ENST00000645124.1:c.*101+1326T>A
ENST00000646020.1:c.*594+1326T>A
ENST00000318842.11:c.1905+1326T>A
ENST00000339363.7:c.2520+1326T>A
ENST00000378505.6:c.3231T>A
ENST00000465127.1:c.172-380353A>T
ENST00000474584.5:c.*37+5191T>A
ENST00000482855.5:c.1905+1326T>A
ENST00000494707.5:c.139+5191T>A
NM_000328.2:c.1905+1326T>A
NM_001034853.1:c.3231T>A
NM_001367245.1:c.1902+1326T>A
NM_001367246.1:c.1719+1326T>A
NM_001367247.1:c.1572+5191T>A
NM_001367248.1:c.1602+5191T>A
NM_001367249.1:c.1569+5191T>A
NM_001367250.1:c.1569+5191T>A
NM_001367251.1:c.1386+5191T>A
NR_159803.1:n.2263+1326T>A
NR_159804.1:n.1648+5191T>A
NR_159805.1:n.1714+5191T>A
NR_159806.1:n.1866+1326T>A
NR_159807.1:n.1622+5191T>A
NR_159808.1:n.1826+5191T>A
NM_000328.3:c.1905+1326T>A
More

Benign

Met criteria codes 3
BA1 BP4_Strong BS2_Supporting

Evidence Links 0

Expert Panel

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.3231T>A (p.Asn1077Lys) is a missense variant encoding the substitution of asparagine with lysine at position 1077. This variant is present in gnomAD v.4.1.0 at a frequency of 0.02339 among hemizygous individuals, with 9,240 variant alleles / 395,050 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 0.05, 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 0.00, 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). This variant has been reported in at least 2 apparently unrelated control individuals meeting the BS2 requirement of no functional visual impairment by age 30 years (PMIDs: 12657579, BS2_supporting). 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, BP4_strong, and BS2_supporting. (date of approval 05/16/2025).
Met criteria codes
BA1
This variant is present in gnomAD v.4.0.0 at a frequency of 0.02339 among hemizygous individuals, with 9240 variant alleles / 395050 total alleles, which is higher than the ClinGen X-linked IRD VCEP BA1 threshold of >0.00005 (BA1).
BP4_Strong
The computational predictor REVEL gives a score of 0.05, 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 0.00, 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).
BS2_Supporting
This variant has been reported in at least 2 apparently unrelated control individuals meeting the BS2 requirement of no recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder by the age of 30 (PMIDs: 12657579, BS2_Supporting).
Curation History
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