18-13826140-C-A

Variant names:

• chr18-13826140-C-A
• rs45613135
• NM_005913.3:c.375C>A

Variant summary

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

The NM_005913.3(MC5R):​c.375C>A​(p.Ser125Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S125S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MC5R NM_005913.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 0 publications found

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]

ACMG classification

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.375C>A	p.Ser125Ser	synonymous	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.375C>A	p.Ser125Ser	synonymous	Exon 2 of 2	ENSP00000468086.2	P33032
	MC5R	ENST00000324750.5	TSL:6	c.375C>A	p.Ser125Ser	synonymous	Exon 1 of 1	ENSP00000318077.3	P33032

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	1.2
DANN	Benign	0.78
PhyloP100		-1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: 2

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

Other links and lift over

dbSNP: rs45613135; hg19: chr18-13826139;