ACMG SF v3.3 Secondary Findings: What Exome and Genome Labs Must Report
Short answer: ACMG SF v3.3, published in Genetics in Medicine on June 23, 2025, added three genes, ABCD1, CYP27A1 and PLN, to the recommended secondary findings list, bringing it to 84 genes. Labs doing clinical exome or genome sequencing that offer secondary findings should update gene lists, consent language, and QA, because reporting remains optional but list-driven.
What ACMG changed in SF v3.3
The American College of Medical Genetics and Genomics maintains a minimum list of medically actionable genes that laboratories are encouraged to evaluate when performing clinical exome or genome sequencing, even when the indication for testing is unrelated. ACMG first established the list in 2013. Version 3.2 followed in 2023. The 2025 update, SF v3.3, was published in Genetics in Medicine (DOI 10.1016/j.gim.2025.101454) on June 23, 2025, and announced in an ACMG press release dated July 9, 2025.
ACMG describes v3.3 as a minor revision. Under its versioning approach, major revisions involve conceptual changes or many genes added or removed and advance the whole number, such as v4.0, while minor revisions add or remove one or a few genes or variants. The working group said the changes are consistent with its goal of maintaining a minimum list of actionable results.
The three genes added
ACMG added ABCD1, CYP27A1, and PLN. Per Baylor Genetics, which published a test update on its implementation, the associated conditions are adrenoleukodystrophy (ABCD1), cerebrotendinous xanthomatosis (CYP27A1), and dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy (PLN). ACMG says each addition was selected for actionability and potential impact on patient care.
Illumina's Emedgene documentation states that the addition brings the total to 84 reportable genes. Because the three additions are the only gene changes described, the prior v3.2 list works out to 81 genes. That 81 figure is arithmetic from the sources, not a number ACMG states directly, so labs should confirm against the official list.
What was considered and not added
The working group did not simply add everything nominated. It considered GCK, RUNX1, and SLC4A1 and did not add them. It also deferred a decision on ADA2 until additional information is available to inform a vote. ACMG says the working group will keep reviewing the list and accepting nominations throughout the year, so more movement is possible.
For lab directors, the deferred and rejected genes matter as much as the additions. A lab that adds extra genes beyond the ACMG minimum list creates its own reporting obligations and interpretation burden. The minimum list is a floor for what is recommended, and the decision to go beyond it should be deliberate and documented.
A new ClinGen resource for reportability
Alongside the list, ACMG pointed to a new, publicly available ClinGen webpage that helps clinical labs decide whether specific variants, or variants in specific gene-disease pairs, are reportable. ACMG quotes Christa L. Martin as saying it provides guidance for determining whether specific variants or gene-disease pairs are reportable. The page is hosted on the ClinGen knowledge base.
Operationally, this is useful for variant interpretation standard operating procedures. Rather than relying on each analyst's reading of the policy statement, a lab can point to a shared reference when deciding whether a given finding falls inside the list's scope. That consistency also helps when a referring clinician or payer questions why a result was or was not returned.
How one laboratory implemented it
Baylor Genetics published a test update dated January 13, 2026, stating that the change was effective January 12, 2026. It reports that secondary findings remain optional for whole genome and whole exome sequencing, that providers who opt in automatically receive results based on the updated gene list, and that consent requirements, billing, and turnaround time are unchanged. This is one lab's policy and not a universal rule, but it is a useful model of a clean rollout.
Note the lag. The guidance was published in mid-2025, and this laboratory's go-live followed in January 2026. A gap of several months between publication and production reporting is common because it takes time to validate pipelines, update report templates, and revise consent forms. Labs that have not yet moved should treat the gap as a risk to close rather than a norm to extend.
What labs and revenue cycle teams should do now
First, compare the gene list in your analysis pipeline and report templates against SF v3.3, and document the effective date of your cutover. Second, review consent and requisition language so that opt-in and opt-out choices for secondary findings are captured at order entry and carried into the report. Third, confirm that your variant classification workflow covers the three new genes, including interpretation of findings in ABCD1, CYP27A1, and PLN.
Fourth, coordinate with ordering clinicians and genetic counselors. Pretest counseling for exome and genome sequencing already addresses variants of uncertain significance and incidental findings, a theme we covered in our analysis of exome sequencing coverage for developmental delay. Adding genes to the list changes what a family might hear back, so counseling scripts should be refreshed.
Fifth, check how downstream billing and documentation connect. Secondary findings reporting is typically part of the same sequencing service, and Baylor reports no billing change for its implementation, but diagnosis coding and medical necessity documentation should still be driven by the primary indication. Our guides on genetic testing denials and ICD-10 codes for genetic testing cover the claim side, and our overview of NCCN hereditary cancer testing guidelines shows how another body of guidance feeds into medical necessity. For more resources, visit the ScreenMyGene homepage.
Risks to manage
The main risks are inconsistency and silent drift. If different report templates, pipelines, or sites use different list versions, two patients with the same variant may receive different results. Version control for the gene list, with a named owner and a review cadence tied to ACMG announcements, is a low-cost safeguard. Because ACMG accepts nominations year-round, assign someone to watch for the next revision rather than waiting for a customer to ask.
Frequently asked questions
Is reporting ACMG secondary findings mandatory?
ACMG recommends laboratories evaluate the listed genes when performing clinical exome or genome sequencing. In practice, offering results is often opt-in. Baylor Genetics, for example, states that secondary findings remain optional and that providers who opt in receive results based on the updated list. Check your own lab policy and consent process.
Which genes did SF v3.3 add?
SF v3.3 added ABCD1, CYP27A1, and PLN. Baylor Genetics associates them with adrenoleukodystrophy, cerebrotendinous xanthomatosis, and dilated cardiomyopathy with arrhythmogenic right ventricular cardiomyopathy, respectively. ACMG says each was selected for actionability and potential impact on patient care. Illumina documentation reports the total is now 84 reportable genes.
What happened to GCK, RUNX1, SLC4A1, and ADA2?
ACMG considered GCK, RUNX1, and SLC4A1 and did not add them. It deferred a decision on ADA2 until additional information is available to inform a vote. The working group says it will keep reviewing the list and accepting nominations throughout the year, so these decisions could be revisited in later revisions.
Does the update change billing for exome or genome sequencing?
The sources reviewed do not describe a payer or coding change from SF v3.3. Baylor Genetics reports that billing is unchanged for its implementation. Billing rules are payer-specific, so labs should verify with each payer and keep claims tied to the primary clinical indication for testing.
Where can labs check whether a variant is reportable?
ACMG highlighted a new public ClinGen webpage that provides guidance on whether specific variants or variants in specific gene-disease pairs are reportable under the SF list. Labs can incorporate it into variant interpretation procedures alongside their own classification policies and the ACMG policy statement itself.
Educational disclaimer: This article is provided for informational and educational purposes only and is intended for laboratory, billing, and clinical operations professionals. It is not medical, legal, coding, or reimbursement advice and does not recommend testing for any individual patient. Verify current requirements with ACMG, your accrediting body, and each payer.
Sources: ACMG, "ACMG Releases 2025 Update to Secondary Findings Gene List," July 9, 2025; ACMG SF v3.3 policy statement, Genetics in Medicine, DOI 10.1016/j.gim.2025.101454, June 23, 2025; Baylor Genetics, "Updates to Reporting of the ACMG Secondary Findings v3.3 List," January 13, 2026; Illumina Emedgene manual, Incidental (secondary) findings.