Submissions for variant NM_017849.4(TMEM127):c.621G>A (p.Ala207=)

gnomAD frequency: 0.13717  dbSNP: rs3852673

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039051	SCV000062729	benign	not specified	2012-12-21	criteria provided, single submitter	clinical testing	Ala207Ala in exon 4 of TMEM127: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified identified in 11.5% o f chromosomes from a broad, though clinically and racially unspecified populatio n by the 1000 Genomes project (dbSNP rs3852673). Ala207Ala in exon 4 of TMEM127 (rs3852673; allele frequency = 11.5%)
Ambry Genetics	RCV000162443	SCV000212793	benign	Hereditary cancer-predisposing syndrome	2014-11-18	criteria provided, single submitter	clinical testing	This alteration is classified as 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	RCV000039051	SCV000313041	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000280717	SCV000432538	benign	Pheochromocytoma	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588500	SCV000699443	benign	not provided	2016-05-26	criteria provided, single submitter	clinical testing	Variant summary: The TMEM127 c.621G>A (p.Ala207Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts polymorphism outcome for this variant. 5/5 Alamut algorithms predict no significant change to normal splicing. This variant was found in 19810/121224 control chromosomes (1938 homozygotes) at a frequency of 0.1634165, which greatly exceeds the estimated maximal expected allele frequency of a pathogenic TMEM127 variant (0.0000001), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as Benign. Taken together and based on the high allele frequency in the general population, this variant is classified as Benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001513083	SCV001720617	benign	Hereditary pheochromocytoma-paraganglioma	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000588500	SCV001833525	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000280717	SCV004015617	benign	Pheochromocytoma	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000588500	SCV005245797	benign	not provided		criteria provided, single submitter	not provided
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000039051	SCV001928227	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000039051	SCV001959530	benign	not specified		no assertion criteria provided	clinical testing