rs138015501

Variant names:

• chr6-99943102-C-G
• 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. Variant got 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

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCHR2	NM_001040179.2	c.434G>C	p.Arg145Thr	missense_variant	Exon 4 of 6	ENST00000281806.7	NP_001035269.1
MCHR2	NM_032503.3	c.434G>C	p.Arg145Thr	missense_variant	Exon 4 of 6		NP_115892.2
MCHR2	XM_024446571.2	c.434G>C	p.Arg145Thr	missense_variant	Exon 4 of 6		XP_024302339.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCHR2	ENST00000281806.7	c.434G>C	p.Arg145Thr	missense_variant	Exon 4 of 6	2	NM_001040179.2	ENSP00000281806.2
MCHR2	ENST00000369212.2	c.434G>C	p.Arg145Thr	missense_variant	Exon 4 of 6	1		ENSP00000358214.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;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;D
MetaSVM	Benign	-0.44	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-5.4	D;D
REVEL	Uncertain	0.53
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.74
MutPred		0.71		Loss of methylation at R145 (P = 0.0182);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-100390978;