ClinVar Miner

Submissions for variant NM_005912.3(MC4R):c.63_64del (p.Tyr21_Arg22delinsTer)

dbSNP: rs770293321
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Institute Rare Disease Group, Broad Institute RCV000582390 SCV001422869 uncertain significance Obesity 2020-01-22 criteria provided, single submitter curation The p.Tyr21Terfs variant in MC4R has not been previously reported in individuals with obesity and has been identified in 0.007% (2/30616) of South Asian chromosomes and 0.006% (1/16150) African chromosomes by the Genome Aggregation Database (gnomAD,; dbSNP rs770293321). This variant has also been reported in ClinVar (Variation ID: 492860). This variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at position 21 and leads to a premature termination codon at the same position. This alteration is then predicted to lead to a truncated protein since this is a single exon gene that is not predicted to undergo nonsense mediated decay. Heterozygous loss of function of the MC4R gene is an established disease mechanism in obesity. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PVS1_moderate, PM2_supporting (Richards 2015).
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000582390 SCV000692293 pathogenic Obesity 2016-09-08 no assertion criteria provided clinical testing
PerkinElmer Genomics RCV001783088 SCV002022762 likely pathogenic BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 20 2021-01-19 no assertion criteria provided clinical testing

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