Submissions for variant NM_014423.4(AFF4):c.3242C>G (p.Ser1081Cys)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003752990	SCV004518137	uncertain significance	Cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome	2023-04-06	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1081 of the AFF4 protein (p.Ser1081Cys). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt AFF4 protein function. This variant has not been reported in the literature in individuals affected with AFF4-related conditions. This variant is present in population databases (rs772721392, gnomAD 0.002%).
PreventionGenetics, part of Exact Sciences	RCV004750419	SCV005343335	uncertain significance	AFF4-related disorder	2024-09-06	no assertion criteria provided	clinical testing	The AFF4 c.3242C>G variant is predicted to result in the amino acid substitution p.Ser1081Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.