rs3827103

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_019888.3(MC3R):c.130G>A(p.Val44Ile) variant causes a missense change. The variant allele was found at a frequency of 0.114 in 1,613,936 control chromosomes in the GnomAD database, including 15,923 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 4424 hom., cov: 32)

Exomes 𝑓: 0.11 ( 11499 hom. )

Consequence

MC3R
NM_019888.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 6.66

Publications

46 publications found

Variant links:

Genes affected

MC3R (HGNC:6931): (melanocortin 3 receptor) This gene encodes a G-protein-coupled receptor for melanocyte-stimulating hormone and adrenocorticotropic hormone that is expressed in tissues other than the adrenal cortex and melanocytes. This gene maps to the same region as the locus for benign neonatal epilepsy. Mice deficient for this gene have increased fat mass despite decreased food intake, suggesting a role for this gene product in the regulation of energy homeostasis. Mutations in this gene are associated with a susceptibility to obesity in humans. [provided by RefSeq, Jul 2008]

MC3R Gene-Disease associations (from GenCC):

body mass index quantitative trait locus 9
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

MC3R links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050959885).

BP6

Variant 20-56248973-G-A is Benign according to our data. Variant chr20-56248973-G-A is described in ClinVar as Benign. ClinVar VariationId is 1227705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MC3R	NM_019888.3 link	c.130G>A	p.Val44Ile	missense_variant	Exon 1 of 1	ENST00000243911.2	NP_063941.3	P41968

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MC3R	ENST00000243911.2 link	c.130G>A	p.Val44Ile	missense_variant	Exon 1 of 1	6	NM_019888.3	ENSP00000243911.2		P41968

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

29030

AN:

151956

Hom.:

4404

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.0956

Gnomad EAS

AF:

0.236

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.0924

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.0859

Gnomad OTH

AF:

0.147

GnomAD2 exomes

AF:

0.136

AC:

34155

AN:

250886

AF XY:

0.134

show subpopulations

Gnomad AFR exome

AF:

0.432

Gnomad AMR exome

AF:

0.0905

Gnomad ASJ exome

AF:

0.0853

Gnomad EAS exome

AF:

0.231

Gnomad FIN exome

AF:

0.0909

Gnomad NFE exome

AF:

0.0871

Gnomad OTH exome

AF:

0.116

GnomAD4 exome

AF:

0.106

AC:

154810

AN:

1461862

Hom.:

11499

Cov.:

AF XY:

0.108

AC XY:

78500

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.434

AC:

14547

AN:

33480

American (AMR)

AF:

0.0908

AC:

4063

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0880

AC:

2299

AN:

26136

East Asian (EAS)

AF:

0.239

AC:

9487

AN:

39698

South Asian (SAS)

AF:

0.207

AC:

17819

AN:

86258

European-Finnish (FIN)

AF:

0.0949

AC:

5069

AN:

53396

Middle Eastern (MID)

AF:

0.150

AC:

866

AN:

5768

European-Non Finnish (NFE)

AF:

0.0837

AC:

93120

AN:

1112006

Other (OTH)

AF:

0.125

AC:

7540

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

9441

18881

28322

37762

47203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3744

7488

11232

14976

18720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.191

AC:

29107

AN:

152074

Hom.:

4424

Cov.:

AF XY:

0.190

AC XY:

14110

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.423

AC:

17560

AN:

41474

American (AMR)

AF:

0.111

AC:

1694

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0956

AC:

332

AN:

3472

East Asian (EAS)

AF:

0.235

AC:

1213

AN:

5154

South Asian (SAS)

AF:

0.208

AC:

1002

AN:

4810

European-Finnish (FIN)

AF:

0.0924

AC:

978

AN:

10580

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0859

AC:

5843

AN:

67992

Other (OTH)

AF:

0.152

AC:

321

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1028

2056

3084

4112

5140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.117

Hom.:

7918

Bravo

AF:

0.201

TwinsUK

AF:

0.0804

AC:

298

ALSPAC

AF:

0.0848

AC:

327

ESP6500AA

AF:

0.419

AC:

1845

ESP6500EA

AF:

0.0865

AC:

744

ExAC

AF:

0.145

AC:

17635

Asia WGS

AF:

0.244

AC:

847

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 24, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 24487982, 26818770, 16123355) -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.029

Eigen

Benign

0.048

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.92

MetaRNN

Benign

0.0051

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.83

PhyloP100

6.7

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.14

REVEL

Benign

0.089

Sift

Benign

0.049

Sift4G

Benign

0.19

Vest4

0.058

MPC

0.20

ClinPred

0.042

GERP RS

4.0

PromoterAI

0.023

Neutral

(source)

Varity_R

0.088

gMVP

0.55

Mutation Taster

=86/14

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over