Submissions for variant NM_020223.4(FAM20C):c.252C>A (p.Asn84Lys)

gnomAD frequency: 0.00178  dbSNP: rs190382829

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000224835	SCV000281016	uncertain significance	not provided	2015-06-04	criteria provided, single submitter	clinical testing	Converted during submission to Uncertain significance.
Eurofins Ntd Llc (ga)	RCV000224835	SCV000707882	uncertain significance	not provided	2017-04-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000224835	SCV002200404	uncertain significance	not provided	2022-10-07	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 84 of the FAM20C protein (p.Asn84Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with FAM20C-related conditions. ClinVar contains an entry for this variant (Variation ID: 235432). 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: "Benign"; Align-GVGD: "Class C0"). 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.
Breakthrough Genomics, Breakthrough Genomics	RCV000224835	SCV005189352	uncertain significance	not provided		criteria provided, single submitter	not provided
Ambry Genetics	RCV004975335	SCV005584682	likely benign	Inborn genetic diseases	2024-10-09	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003907835	SCV004718655	likely benign	FAM20C-related disorder	2019-07-29	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).