Genetic Variant MC5R:p.Thr184Ile (chr18-13826316-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005913.3(MC5R):c.551C>T(p.Thr184Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

MC5R
NM_005913.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.97

Publications

1 publications found

Variant links:

Genes affected

MC5R (HGNC:6933): (melanocortin 5 receptor) This gene encodes a member of the seven-pass transmembrane G protein-coupled melanocortin receptor protein family that stimulate cAMP signal transduction. The encoded protein is a receptor for melanocyte-stimulating hormone and adrenocorticotropic hormone and is suggested to play a role in sebum generation. [provided by RefSeq, Jun 2010]

MC5R links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005913.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MC5R	NM_005913.3	MANE Select	c.551C>T	p.Thr184Ile	missense	Exon 2 of 2	NP_005904.1	P33032

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MC5R	ENST00000589410.2	TSL:3 MANE Select	c.551C>T	p.Thr184Ile	missense	Exon 2 of 2	ENSP00000468086.2	P33032
	MC5R	ENST00000324750.5	TSL:6	c.551C>T	p.Thr184Ile	missense	Exon 1 of 1	ENSP00000318077.3	P33032

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000239

AC:

AN:

251466

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461820

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000894

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.0000812

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1112008

Other (OTH)

AF:

0.0000828

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

Eigen

Benign

0.041

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0083

MetaRNN

Uncertain

0.46

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.6

PhyloP100

3.0

PrimateAI

Uncertain

0.48

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.19

Sift

Uncertain

0.0090

Sift4G

Benign

0.14

Polyphen

0.98

Vest4

0.66

MutPred

0.57

Loss of glycosylation at T184 (P = 0.1079)

MVP

0.70

MPC

0.78

ClinPred

0.48

GERP RS

2.0

Varity_R

0.22

Mutation Taster

=78/22

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over