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_000330.4(RS1):c.330T>C (p.Cys110=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA226691

98940 (ClinVar)

Gene: RS1

Condition: X-linked retinoschisis

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 1e9db832-f26c-487e-bd00-49a1b7b7f7c1

Approved on: 2025-05-19

Published on: 2025-05-20

HGVS expressions

NM_000330.4:c.330T>C

NM_000330.4(RS1):c.330T>C (p.Cys110=)

NC_000023.11:g.18644622A>G

CM000685.2:g.18644622A>G

NC_000023.10:g.18662742A>G

CM000685.1:g.18662742A>G

NC_000023.9:g.18572663A>G

NG_008475.1:g.224018A>G

NG_008659.3:g.37827T>C

ENST00000379984.4:c.330T>C

ENST00000379984.3:c.330T>C

ENST00000379989.6:c.2714-1385A>G

ENST00000379996.7:c.2714-1385A>G

ENST00000476595.1:n.821T>C

NM_000330.3:c.330T>C

NM_001037343.1:c.2714-1385A>G

NM_003159.2:c.2714-1385A>G

NM_001037343.2:c.2714-1385A>G

NM_003159.3:c.2714-1385A>G

Benign

BP7 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 RS1 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

X-linked Inherited Retinal Disease VCEP

The NM_000330.4(RS1):c.330T>C variant is a synonymous variant at amino acid 110. This variant is present in gnomAD v.4.1.0 at a frequency of 0.01431 among hemizygous individuals, with 5657 variant alleles / 395399 total hemizygous alleles, which is higher than the ClinGen X-linked IRD VCEP BA1 threshold of >0.0002 (BA1). The splicing impact predictor SpliceAI gives a delta score of 0.00 for all predictive splice changes, which is below the ClinGen X-linked IRD VCEP recommended threshold of <0.1 and does not strongly predict an impact on splicing (BP4). This silent variant c.330T>C causing a synonymous variant at codon 110 does not have an impact at splicing sites according to Splice AI, which predicts a delta score of 0.00 for all predictive splice changes which is below the ClinGen X-linked IRD VCEP recommended threshold of <0.1 and does not strongly predict an impact on splicing (BP7). 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, BP4, and BP7 (date of approval 01/24/2025).

BP7

This silent variant c.330T>C causing a synonymous variant at codon 110 does not have an impact at splicing sites according to Splice AI, which predicts a delta score of 0.00 for all predictive splice changes which is below the ClinGen X-linked IRD VCEP recommended threshold of <0.1 and does not strongly predict an impact on RS1 splicing (BP7).

BP4

The splicing impact predictor SpliceAI gives a delta score of 0.00 for all predictive splice changes, which is below the ClinGen X-linked IRD VCEP recommended threshold of <0.1 and does not strongly predict an impact on RS1 splicing (BP4).

BA1

This variant is present in gnomAD v.4.1.0 at a frequency of 0.01431 among hemizygous individuals, with 5657 variant alleles / 395399 total hemizygous alleles, which is higher than the ClinGen X-linked IRD VCEP BA1 threshold of >0.0002 (BA1).

Curation History

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