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.177T>C (p.Cys59=)

CA515477887

1541778 (ClinVar)

Gene: RS1 (HGNC:6247)

Condition: X-linked retinoschisis (MONDO:0010725)

Inheritance Mode: X-linked inheritance (recessive (HP:0001419))

UUID: f6ace292-1671-4377-b486-c8abc2aaf55b

Approved on: 2025-09-23

Published on: 2025-09-23

HGVS expressions

NM_000330.4(RS1):c.177T>C (p.Cys59=)

NM_000330.4:c.177T>C

NC_000023.11:g.18656660A>G

CM000685.2:g.18656660A>G

NC_000023.10:g.18674780A>G

CM000685.1:g.18674780A>G

NC_000023.9:g.18584701A>G

NG_008659.3:g.25789T>C

ENST00000379984.4:c.177T>C

ENST00000379984.3:c.177T>C

NM_000330.3:c.177T>C

Likely Benign

BP4 BP7

PM2 BS1

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

NM_000330.4(RS1):c.177T>C (p.Cys59=) is a synonymous variant at amino acid 59, within exon 3, and does not have predicted splicing impact (BP7). 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). This variant is present in gnomAD v4.1.0 at a frequency of 0.000007745 among hemizygous individuals, with 3 variant alleles / 387,371 total alleles, which is between the ClinGen X-linked IRD VCEP PM2_Supporting threshold of <0.000002 and BS1 threshold of >0.00002 and fails to meet these criteria. In summary, this variant is classified as likely 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: BP4 and BP7.

BP4

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).

BP7

This silent variant c.177T>C causing a synonymous variant at codon 59 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).

PM2

This variant is present in gnomAD v4.1.0 at a frequency of 0.000007745 among hemizygous individuals, with 3 variant alleles / 387,371 total alleles, which is between the ClinGen X-linked IRD VCEP PM2_Supporting threshold of <0.000002 and BS1 threshold of >0.00002 and fails to meet these criteria.

BS1

Curation History

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