NM_002386.4(MC1R):c.415G>A (p.Ala139Thr) AND Melanoma, cutaneous malignant, susceptibility to, 5

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 25, 2021
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:: RCV002043190.6

Allele description [Variation Report for NM_002386.4(MC1R):c.415G>A (p.Ala139Thr)]

NM_002386.4(MC1R):c.415G>A (p.Ala139Thr)

Gene:

MC1R:melanocortin 1 receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_002386.4(MC1R):c.415G>A (p.Ala139Thr)

HGVS:

NC_000016.10:g.89919673G>A
NG_012026.1:g.6795G>A
NG_027810.1:g.2665G>A
NM_002386.4:c.415G>AMANE SELECT
NP_002377.4:p.Ala139Thr
NC_000016.9:g.89986081G>A

Protein change:

A139T

Links:

dbSNP: rs765120108

NCBI 1000 Genomes Browser:

rs765120108

Molecular consequence:

NM_002386.4:c.415G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Melanoma, cutaneous malignant, susceptibility to, 5
Synonyms:: Cutaneous malignant melanoma 5
Identifiers:: MONDO: MONDO:0013133; MedGen: C2751295; Orphanet: 618; OMIM: 613099

Recent activity

Clear Turn Off Turn On

Mus musculus protein phosphatase 1J (Ppm1j), mRNA
Mus musculus protein phosphatase 1J (Ppm1j), mRNA
gi|114205423|ref|NM_027982.2|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002307491	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 25, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19585506, 24982914, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002307491

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 25, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Melanocortin receptor 1 variants and melanoma risk: a study of 2 European populations.

Scherer D, Nagore E, Bermejo JL, Figl A, Botella-Estrada R, Thirumaran RK, Angelini S, Hemminki K, Schadendorf D, Kumar R.

Int J Cancer. 2009 Oct 15;125(8):1868-75. doi: 10.1002/ijc.24548.

PubMed [citation]

PMID:: 19585506

A large French case-control study emphasizes the role of rare Mc1R variants in melanoma risk.

Hu HH, Benfodda M, Dumaz N, Gazal S, Descamps V, Bourillon A, Basset-Seguin N, Riffault A, Ezzedine K, Bagot M, Bensussan A, Saiag P, Grandchamp B, Soufir N.

Biomed Res Int. 2014;2014:925716. doi: 10.1155/2014/925716. Epub 2014 Apr 10.

PubMed [citation]

PMID:: 24982914
PMCID:: PMC4003837

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002307491.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with melanoma (PMID: 19585506, 24982914). This variant is present in population databases (rs765120108, ExAC 0.002%). This sequence change replaces alanine with threonine at codon 139 of the MC1R protein (p.Ala139Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine.

#	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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine