ClinVar Miner

Submissions for variant NM_004990.4(MARS1):c.747G>A (p.Pro249=)

gnomAD frequency: 0.00004  dbSNP: rs200490364
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000513080 SCV000608653 uncertain significance not provided 2017-06-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000557196 SCV000655645 likely benign Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U 2024-03-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV004023460 SCV002755163 likely benign not specified 2019-07-11 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004023460 SCV005884012 likely benign not specified 2024-12-11 criteria provided, single submitter clinical testing Variant summary: MARS1 c.747G>A alters a non-conserved nucleotide resulting in a synonymous change. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 3.4e-05 in 1606926 control chromosomes in the gnomAD database (v4.1 dataset). This frequency is not significantly higher than estimated for a pathogenic variant in MARS1 causing Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency (0.0011), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.747G>A in individuals affected with Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 444298). Based on the evidence outlined above, the variant was classified as likely benign.

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