20-56249030-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_019888.3(MC3R):c.187G>A(p.Val63Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000657 in 1,614,032 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000069 ( 2 hom. )
Consequence
MC3R
NM_019888.3 missense
NM_019888.3 missense
Scores
5
4
10
Clinical Significance
Conservation
PhyloP100: 4.81
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.37502402).
BS2
?
High AC in GnomAd at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MC3R | NM_019888.3 | c.187G>A | p.Val63Met | missense_variant | 1/1 | ENST00000243911.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MC3R | ENST00000243911.2 | c.187G>A | p.Val63Met | missense_variant | 1/1 | NM_019888.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152176Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000796 AC: 20AN: 251174Hom.: 1 AF XY: 0.0000884 AC XY: 12AN XY: 135732
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GnomAD4 exome AF: 0.0000691 AC: 101AN: 1461856Hom.: 2 Cov.: 33 AF XY: 0.0000853 AC XY: 62AN XY: 727230
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152176Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74338
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
MC3R-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 20, 2024 | The MC3R c.187G>A variant is predicted to result in the amino acid substitution p.Val63Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.049% of alleles in individuals of South Asian descent in gnomAD, including a homozygous individual. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at