ClinVar Miner

Submissions for variant NM_020191.4(MRPS22):c.509G>A (p.Arg170His)

gnomAD frequency: 0.00012  dbSNP: rs119478059
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000799575 SCV000939245 pathogenic not provided 2021-08-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 170 of the MRPS22 protein (p.Arg170His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs119478059, ExAC 0.01%). This missense change has been observed in individual(s) with MRPS22-related disease (PMID: 29096039; 17873122and29096039). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4753). 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: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects MRPS22 function (PMID: 17873122, 18539099). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002496263 SCV002811433 likely pathogenic Hypotonia with lactic acidemia and hyperammonemia; Ovarian dysgenesis 7 2022-03-22 criteria provided, single submitter clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000005019 SCV003843201 likely pathogenic Hypotonia with lactic acidemia and hyperammonemia 2019-10-01 criteria provided, single submitter clinical testing This variant was observed in compound heterozygosity with variant c.480_481insA
GeneDx RCV000799575 SCV003929735 likely pathogenic not provided 2024-01-02 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 18539099, 29096039, 31683770, 17873122, 31589614, 33917098, 33314036, 37035737, 38012047)
OMIM RCV000005019 SCV000025195 pathogenic Hypotonia with lactic acidemia and hyperammonemia 2007-12-01 no assertion criteria provided literature only

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