NM_005912.3(MC4R):c.466C>T (p.Gln156Ter) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Aug 31, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000681814.4

Allele description [Variation Report for NM_005912.3(MC4R):c.466C>T (p.Gln156Ter)]

NM_005912.3(MC4R):c.466C>T (p.Gln156Ter)

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.466C>T (p.Gln156Ter)

HGVS:

NC_000018.10:g.60371884G>A
NG_016441.1:g.5885C>T
NM_005912.3:c.466C>TMANE SELECT
NP_005903.2:p.Gln156Ter
LRG_1346t1:c.466C>T
LRG_1346:g.5885C>T
LRG_1346p1:p.Gln156Ter
NC_000018.9:g.58039117G>A
NM_005912.2:c.466C>T

Protein change:

Q156*

Links:

dbSNP: rs369841551

NCBI 1000 Genomes Browser:

rs369841551

Molecular consequence:

NM_005912.3:c.466C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000809285	Gharavi Laboratory, Columbia University	no assertion criteria provided (ACMG Guidelines, 2015)	Likely pathogenic (Sep 16, 2018)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV000842716	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Feb 19, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27654141, 26467025
SCV005328147	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Aug 31, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000809285

Gharavi Laboratory, Columbia University

no assertion criteria provided

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 16, 2018)

germline

research

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

SCV000842716

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(Feb 19, 2018)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV005328147

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Aug 31, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing, research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

Prevalence and phenotypic characterization of MC4R variants in a large pediatric cohort.

Vollbach H, Brandt S, Lahr G, Denzer C, von Schnurbein J, Debatin KM, Wabitsch M.

Int J Obes (Lond). 2017 Jan;41(1):13-22. doi: 10.1038/ijo.2016.161. Epub 2016 Sep 22.

PubMed [citation]

PMID:: 27654141

See all PubMed Citations (3)

Details of each submission

From Gharavi Laboratory, Columbia University, SCV000809285.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Athena Diagnostics, SCV000842716.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV005328147.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Identified in the heterozygous state in individuals with obesity in the published literature, however segregation studies were not completed (Vollbach et al., 2017; Namjou et al., 2021); Identified in an individual with kidney disease in the published literature, and information on body mass index was not provided (Groopman et al., 2019); Nonsense variant predicted to result in protein truncation, as the last 177 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31447099, 27654141, 29568105, 32952152, 30586318)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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