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NM_005912.3(MC4R):c.983T>A (p.Leu328Ter) AND MC4R-related disorder

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 19, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003411650.4

Allele description [Variation Report for NM_005912.3(MC4R):c.983T>A (p.Leu328Ter)]

NM_005912.3(MC4R):c.983T>A (p.Leu328Ter)

Gene:
MC4R:melanocortin 4 receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
18q21.32
Genomic location:
Preferred name:
NM_005912.3(MC4R):c.983T>A (p.Leu328Ter)
HGVS:
  • NC_000018.10:g.60371367A>T
  • NG_016441.1:g.6402T>A
  • NM_005912.3:c.983T>AMANE SELECT
  • NP_005903.2:p.Leu328Ter
  • LRG_1346t1:c.983T>A
  • LRG_1346:g.6402T>A
  • LRG_1346p1:p.Leu328Ter
  • NC_000018.9:g.58038600A>T
  • NM_005912.2:c.983T>A
Protein change:
L328*
Links:
dbSNP: rs751914635
NCBI 1000 Genomes Browser:
rs751914635
Molecular consequence:
  • NM_005912.3:c.983T>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
MC4R-related disorder
Synonyms:
MC4R-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004111733PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Sep 19, 2022) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004111733.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The MC4R c.983T>A variant is predicted to result in premature protein termination (p.Leu328*). This variant truncates the final five amino acids of the MC4R protein. To our knowledge, this variant has not been reported in individuals with MC4R-related disease. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/18-58038600-A-T). Although truncating variants are expected to be pathogenic, to our knowledge, all are located upstream of this variant. In ClinVar, this variant has been interpreted as pathogenic (https://ncbi.nlm.nih.gov/clinvar/variation/586139/). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 19, 2024