Submissions for variant NM_020191.4(MRPS22):c.741C>G (p.His247Gln)

gnomAD frequency: 0.00357  dbSNP: rs140631494

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000757468	SCV000885708	likely benign	not provided	2017-09-15	criteria provided, single submitter	clinical testing	The p.His247Gln variant (rs140631494) has not been previously associated with any mitochondrial disorder and is listed in the Genome Aggregation Database (gnomAD) browser with a frequency in European populations of 0.7% (identified in 1074 out of 152,296 chromosomes, including 5 homozygotes). Additionally, this variant affects a moderately conserved amino acid (Alamut software v 2.9), and is not predicted to alter MRPS22 structure function (SIFT: tolerated, PolyPhen2: benign, MutationTaster: polymorphism). Therefore, the p.His247Gln variant is likely to be benign.
Invitae	RCV000757468	SCV001031672	benign	not provided	2024-01-22	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001144320	SCV001304912	likely benign	Hypotonia with lactic acidemia and hyperammonemia	2018-01-13	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
CeGaT Center for Human Genetics Tuebingen	RCV000757468	SCV004155627	likely benign	not provided	2023-08-01	criteria provided, single submitter	clinical testing	MRPS22: BS2
PreventionGenetics, part of Exact Sciences	RCV003937737	SCV004751035	benign	MRPS22-related disorder	2019-04-09	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).