ClinVar Miner

Submissions for variant NM_001291303.3(FAT4):c.10643A>G (p.Tyr3548Cys)

gnomAD frequency: 0.00015  dbSNP: rs79726583
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001927902 SCV002173504 uncertain significance not provided 2022-03-28 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 3546 of the FAT4 protein (p.Tyr3546Cys). This variant is present in population databases (rs79726583, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with FAT4-related conditions. 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 FAT4 protein function. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV002074434 SCV002495762 uncertain significance Van Maldergem syndrome 2; Hennekam lymphangiectasia-lymphedema syndrome 2 2021-12-03 criteria provided, single submitter clinical testing FAT4 NM_024582.3 exon 10 p.Tyr3546Cys (c.10637A>G): This variant has not been reported in the literature but is present in 0.05% (23/41438) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/4-125451653-A-G?dataset=gnomad_r3). Evolutionary conservation for this variant is unclear; computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Ambry Genetics RCV003348603 SCV004075575 uncertain significance Inborn genetic diseases 2023-06-16 criteria provided, single submitter clinical testing The c.10637A>G (p.Y3546C) alteration is located in exon 9 (coding exon 9) of the FAT4 gene. This alteration results from a A to G substitution at nucleotide position 10637, causing the tyrosine (Y) at amino acid position 3546 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV001927902 SCV004234762 uncertain significance not provided 2023-05-31 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002074434 SCV005657554 uncertain significance Van Maldergem syndrome 2; Hennekam lymphangiectasia-lymphedema syndrome 2 2024-05-31 criteria provided, single submitter clinical testing

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