Submissions for variant NM_001173990.3(TMEM216):c.277G>A (p.Val93Met)

gnomAD frequency: 0.00004  dbSNP: rs541257103

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000366908	SCV000343312	uncertain significance	not provided	2016-06-21	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001342994	SCV001536947	uncertain significance	Familial aplasia of the vermis	2022-10-17	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 93 of the TMEM216 protein (p.Val93Met). This variant is present in population databases (rs541257103, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with TMEM216-related conditions. ClinVar contains an entry for this variant (Variation ID: 289040). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
GeneDx	RCV000366908	SCV001771352	uncertain significance	not provided	2024-02-25	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics	RCV005049520	SCV005683853	uncertain significance	Joubert syndrome 2; Meckel syndrome, type 2	2024-01-16	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001828263	SCV002091645	uncertain significance	Joubert syndrome 2	2020-02-27	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004734943	SCV005364934	uncertain significance	TMEM216-related disorder	2024-08-07	no assertion criteria provided	clinical testing	The TMEM216 c.277G>A variant is predicted to result in the amino acid substitution p.Val93Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.039% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.