Submissions for variant NM_020937.4(FANCM):c.1097G>A (p.Ser366Asn)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002972120	SCV003285075	uncertain significance	Fanconi anemia	2022-08-21	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with FANCM-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 366 of the FANCM protein (p.Ser366Asn).
PreventionGenetics, part of Exact Sciences	RCV004536498	SCV004116539	uncertain significance	FANCM-related disorder	2023-04-19	criteria provided, single submitter	clinical testing	The FANCM c.1097G>A variant is predicted to result in the amino acid substitution p.Ser366Asn. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0026% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/14-45623169-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.