rs200040661

Variant names:

• chr6-99943109-G-A
• rs200040661
• NM_001040179.2:c.427C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040179.2(MCHR2):​c.427C>T​(p.Arg143Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000534 in 1,610,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: MCHR2 NM_001040179.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22678956).

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.427C>T	p.Arg143Cys	missense	Exon 4 of 6	NP_001035269.1	Q969V1
	MCHR2	NM_032503.3		c.427C>T	p.Arg143Cys	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.427C>T	p.Arg143Cys	missense	Exon 4 of 6	ENSP00000281806.2	Q969V1
	MCHR2	ENST00000369212.2	TSL:1	c.427C>T	p.Arg143Cys	missense	Exon 4 of 6	ENSP00000358214.1	Q969V1
	MCHR2	ENST00000880237.1		c.427C>T	p.Arg143Cys	missense	Exon 4 of 6	ENSP00000550296.1

Frequencies

GnomAD3 genomes AF: 0.0000790 AC: 12 AN: 151956 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000959

GnomAD2 exomes AF: 0.0000360 AC: 9 AN: 250304 AF XY: 0.0000444

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000619

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000507 AC: 74 AN: 1458644 Hom.: 0 Cov.: 30 AF XY: 0.0000524 AC XY: 38 AN XY: 725586

African (AFR) AF: 0.0000599 AC: 2 AN: 33400

American (AMR) AF: 0.0000449 AC: 2 AN: 44586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25998

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 85736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.0000586 AC: 65 AN: 1109938

Other (OTH) AF: 0.0000830 AC: 5 AN: 60256

GnomAD4 genome AF: 0.0000790 AC: 12 AN: 151956 Hom.: 0 Cov.: 31 AF XY: 0.0000674 AC XY: 5 AN XY: 74214

African (AFR) AF: 0.00 AC: 0 AN: 41380

American (AMR) AF: 0.000197 AC: 3 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67982

Other (OTH) AF: 0.000959 AC: 2 AN: 2086

Alfa AF: 0.0000579 Hom.: 0

Bravo AF: 0.000136

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.2
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.086
Sift	Benign	0.033	D
Sift4G	Benign	0.089	T
Polyphen		0.060	B
Vest4		0.37
MVP		0.61
MPC		0.31
ClinPred		0.26	T
GERP RS		3.8
Varity_R		0.13
gMVP		0.22
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs200040661; hg19: chr6-100390985; COSMIC: COSV56000477;