Variant: NM_000330.4(RS1):c.76G>A (p.Glu26Lys)

CA10360819

741219 (ClinVar)

Gene: RS1

Condition: X-linked retinoschisis

Inheritance Mode: X-linked inheritance

UUID: 3b7924ec-034f-46c4-bf24-8513eab3f55c

Approved on: 2025-05-19

Published on: 2025-05-20

HGVS expressions

NM_000330.4:c.76G>A
NM_000330.4(RS1):c.76G>A (p.Glu26Lys)
NC_000023.11:g.18657642C>T
CM000685.2:g.18657642C>T
NC_000023.10:g.18675762C>T
CM000685.1:g.18675762C>T
NC_000023.9:g.18585683C>T
NG_008659.3:g.24807G>A
ENST00000379984.4:c.76G>A
ENST00000379984.3:c.76G>A
NM_000330.3:c.76G>A

Benign

• Met criteria codes: BA1

• Not Met criteria codes: PP3 BP4

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 RS1 Version 1.0.0

Evidence submitted by expert panel

X-linked Inherited Retinal Disease VCEP

The NM_000330.4(RS1):c.76G>A variant is a missense variant encoding the substitution of Glutamic acid with Lysine at amino acid 26. This variant is present in gnomAD v.4.1.0. at a frequency of 0.0004493 among hemizygous individuals, with 174 variant alleles / 387285 total alleles, which is higher than the ClinGen X-linked IRD VCEP BA1 threshold of >0.0002 (BA1). The computational predictor REVEL gives a score of 0.491, which is between the ClinGen X-linked IRD VCEP thresholds of >0.664 and <0.290 and does not predict a damaging effect on RS1 function. Additionally, the splicing impact predictor SpliceAI gives a score of 0.03 (Acceptor Gain), which is below the ClinGen X-linked IRD VCEP recommended threshold of >0.2 and does not strongly predict an impact on splicing. As a result, the BP4 and PP3 codes were not met. In summary, this variant is classified as benign for X-linked retinoschisis based on the ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RS1 Version 1.0.0: BA1. (date of approval 01/24/2025).

Met criteria codes

• BA1: This variant is present in gnomAD v.4.1.0. at a frequency of 0.0004493 among hemizygous individuals, with 174 variant alleles / 387285 total alleles, which is higher than the ClinGen X-linked IRD VCEP BA1 threshold of >0.0002 (BA1).

Not Met criteria codes

• PP3: The computational predictor REVEL gives a score of 0.491, which is below the ClinGen X-linked IRD VCEP threshold of >0.664 and does not predict a damaging effect on RPGR function. Additionally, the splicing impact predictor SpliceAI gives a score of 0.03 (Acceptor Gain), which is below the ClinGen X-linked IRD VCEP recommended threshold of >0.2 and does not strongly predict an impact on splicing.
• BP4: The computational predictor REVEL gives a score of 0.491, which is above the ClinGen X-linked IRD VCEP threshold of <0.290 and does not predict a non-damaging effect on RS1 function.