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_000350.3(ABCA4):c.3G>T (p.Met1Ile)

CA10602781

280328 (ClinVar)

Gene: ABCA4 (HGNC:24)

Condition: ABCA4-related retinopathy (MONDO:0800406)

Inheritance Mode: Autosomal recessive inheritance

UUID: db310fc0-57b0-4838-b622-cd792402c696

Approved on: 2025-12-05

Published on: 2025-12-22

HGVS expressions

NM_000350.3(ABCA4):c.3G>T (p.Met1Ile)

NM_000350.3:c.3G>T

NC_000001.11:g.94121043C>A

CM000663.2:g.94121043C>A

NC_000001.10:g.94586599C>A

CM000663.1:g.94586599C>A

NC_000001.9:g.94359187C>A

NG_009073.1:g.5107G>T

ENST00000370225.4:c.3G>T

ENST00000649773.1:c.3G>T

ENST00000370225.3:c.3G>T

NM_000350.2:c.3G>T

Pathogenic

PM2_Supporting PVS1 PM5

PM3 PS4 PP4

Evidence Links 0

Expert Panel

ABCA4 VCEP

Criteria Specification Information

Criteria Specification: ClinGen ABCA4 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ABCA4 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ABCA4 VCEP

The NM_000350.3:c.3G>T; p.Met1Ile variant in ABCA4 may cause a truncated or absent protein by altering the start codon of the coding sequence and is predicted to lead to the omission of a critical region of the protein (PVS1). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). Another missense variant, c.1A>G; p.Met1Val, in the same codon has been classified as pathogenic for ABCA4-related retinopathy by the ClinGen ABCA4 VCEP (PM5). In summary, this variant meets the criteria to be classified as pathogenic for ABCA4-related retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen ABCA4 VCEP (Specification Version 1.0): PVS1, PM2_Supporting, PM5.

PM2_Supporting

This variant is absent from gnomAD v4.1.0 (PM2_Supporting).

PVS1

The NM_000350.3:c.3G>T (p.Met1Ile) variant in ABCA4 may cause a truncated or absent protein by altering the start codon of the coding sequence and is predicted to lead to the omission of a critical region of the protein (PVS1).

PM5

Another missense variant, c.1A>G (p.Met1Val), ClinVar Variation ID: 99110, in the same codon has been classified as pathogenic for ABCA4-related retinopathy by the ClinGen ABCA4 VCEP, and Splice AI revealed no expected effects on splicing (PM5).

PM3

This variant was seen in compound heterozygosity with c.6383A>G (p.His2128Arg), but the other variant will not be scored as PM3 for the current variant in order to avoid circular logic.

PS4

The prevalence of the variant in affected individuals is not significantly increased compared with the prevalence in controls. The OR is infinity and the CI is 0.31-infinity, however the CI does contain 1 so this code is not applicable.

PP4

This variant has been reported in the literature in an individual with ABCA4-related retinopathy, but they do not meet the PP4 criteria specified by the ABCA4 VCEP (PMID: 37648803).

Curation History

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