ClinVar Miner

Submissions for variant NM_000760.4(CSF3R):c.2069C>T (p.Thr690Met)

gnomAD frequency: 0.00003  dbSNP: rs764345289
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001883965 SCV002146643 uncertain significance Autosomal recessive severe congenital neutropenia due to CSF3R deficiency 2024-12-24 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 690 of the CSF3R protein (p.Thr690Met). This variant is present in population databases (rs764345289, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CSF3R-related conditions. ClinVar contains an entry for this variant (Variation ID: 1379822). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CSF3R protein function with a negative predictive value of 80%. 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.
Genetic Services Laboratory, University of Chicago RCV003151360 SCV003839396 uncertain significance not specified 2022-12-02 no assertion criteria provided clinical testing DNA sequence analysis of the CSF3R gene demonstrated a sequence change, c.2069C>T, in exon 17 that results in an amino acid change, p.Thr690Met. This sequence change does not appear to have been previously described in individuals with CSF3R-related disorders. This sequence change has been described in the gnomAD database with a frequency of 0.003% in the overall population (dbSNP rs764345289). The p.Thr690Met change affects a poorly conserved amino acid residue located in a domain of the CSF3R protein that is not known to be functional. The p.Thr690Met substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Thr690Met change remains unknown at this time.

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