Variant rs3827103 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
MC3R	NM_019888.3 link	c.130G>A	p.Val44Ile	missense_variant	1/1	ENST00000243911.2	NP_063941.3	P41968

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MC3R	ENST00000243911.2 link	c.130G>A	p.Val44Ile	missense_variant	1/1	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

GnomAD3 exomes

AF:

0.136

AC:

34155

AN:

250886

Hom.:

3579

AF XY:

0.134

AC XY:

18131

AN XY:

135602

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 SAS exome

AF:

0.208

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

Gnomad4 AFR exome

AF:

0.434

Gnomad4 AMR exome

AF:

0.0908

Gnomad4 ASJ exome

AF:

0.0880

Gnomad4 EAS exome

AF:

0.239

Gnomad4 SAS exome

AF:

0.207

Gnomad4 FIN exome

AF:

0.0949

Gnomad4 NFE exome

AF:

0.0837

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.191

AC:

29107

AN:

152074

Hom.:

4424

Cov.:

AF XY:

0.190

AC XY:

14110

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.423

Gnomad4 AMR

AF:

0.111

Gnomad4 ASJ

AF:

0.0956

Gnomad4 EAS

AF:

0.235

Gnomad4 SAS

AF:

0.208

Gnomad4 FIN

AF:

0.0924

Gnomad4 NFE

AF:

0.0859

Gnomad4 OTH

AF:

0.152

Alfa

AF:

0.107

Hom.:

3419

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 24, 2019	This variant is associated with the following publications: (PMID: 24487982, 26818770, 16123355) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

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

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

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

Varity_R

0.088

gMVP

0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over