ClinVar Miner

Submissions for variant NM_000939.4(POMC):c.429C>G (p.His143Gln)

gnomAD frequency: 0.00019  dbSNP: rs201519174
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522801 SCV000619842 uncertain significance not provided 2024-07-01 criteria provided, single submitter clinical testing Reported in the heterozygous state in a child and his grandfather with obesity; however, the child's heterozygous parent was not obese, and the H143Q variant was also identified in a control individual (PMID: 16459314); 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: 17578380, 16459314, 19221669)
Illumina Laboratory Services, Illumina RCV001139995 SCV001300200 uncertain significance Obesity 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV001139996 SCV001300201 uncertain significance Obesity due to pro-opiomelanocortin deficiency 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
PreventionGenetics, part of Exact Sciences RCV004537878 SCV004720957 uncertain significance POMC-related disorder 2024-08-22 no assertion criteria provided clinical testing The POMC c.429C>G variant is predicted to result in the amino acid substitution p.His143Gln. This variant has been reported in the heterozygous state in one individual with obesity but was also reported in one control individual (Lee et al. 2006. PubMed ID: 16459314). It was also observed in a cohort of individuals with obesity, and in vitro functional studies show strong evidence of loss of function (Table 3 and Supplemental Data Set, Shah et al. 2023. PubMed ID: 36864747). This variant is reported in 0.033% of alleles in individuals of European (non-Finnish) descent in gnomAD. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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