rs138015501

Variant names:

• chr6-99943102-C-G
• rs138015501
• NM_001040179.2:c.434G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-99943102-C-G
• chr6-99943102-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001040179.2(MCHR2):​c.434G>C​(p.Arg145Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R145K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MCHR2 NM_001040179.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81
• Publications: 0 publications found

Genes affected

MCHR2 (HGNC:20867): (melanin concentrating hormone receptor 2) Predicted to enable G protein-coupled peptide receptor activity. Predicted to be involved in neuropeptide signaling pathway. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.862

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040179.2. 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
	MCHR2	NM_001040179.2	MANE Select	c.434G>C	p.Arg145Thr	missense	Exon 4 of 6	NP_001035269.1	Q969V1
	MCHR2	NM_032503.3		c.434G>C	p.Arg145Thr	missense	Exon 4 of 6	NP_115892.2	Q969V1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCHR2	ENST00000281806.7	TSL:2 MANE Select	c.434G>C	p.Arg145Thr	missense	Exon 4 of 6	ENSP00000281806.2	Q969V1
	MCHR2	ENST00000369212.2	TSL:1	c.434G>C	p.Arg145Thr	missense	Exon 4 of 6	ENSP00000358214.1	Q969V1
	MCHR2	ENST00000880237.1		c.434G>C	p.Arg145Thr	missense	Exon 4 of 6	ENSP00000550296.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459202 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725878

African (AFR) AF: 0.00 AC: 0 AN: 33402

American (AMR) AF: 0.00 AC: 0 AN: 44604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26028

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 85844

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110320

Other (OTH) AF: 0.0000166 AC: 1 AN: 60256

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.44	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.8
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.53
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.74
MutPred		0.71		Loss of methylation at R145 (P = 0.0182)
MVP		0.88
MPC		0.47
ClinPred		1.0	D
GERP RS		4.1
Varity_R		0.92
gMVP		0.63
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs138015501; hg19: chr6-100390978;