6-99943075-T-G

Variant names:

• chr6-99943075-T-G
• rs199973343
• NM_001040179.2:c.461A>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001040179.2(MCHR2):​c.461A>C​(p.Asn154Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. N154S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MCHR2 NM_001040179.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.05
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.803

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.461A>C	p.Asn154Thr	missense	Exon 4 of 6	NP_001035269.1	Q969V1
	MCHR2	NM_032503.3		c.461A>C	p.Asn154Thr	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.461A>C	p.Asn154Thr	missense	Exon 4 of 6	ENSP00000281806.2	Q969V1
	MCHR2	ENST00000369212.2	TSL:1	c.461A>C	p.Asn154Thr	missense	Exon 4 of 6	ENSP00000358214.1	Q969V1
	MCHR2	ENST00000880237.1		c.461A>C	p.Asn154Thr	missense	Exon 4 of 6	ENSP00000550296.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.013	T
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	2.0	M
PhyloP100		5.1
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.37
Sift	Benign	0.063	T
Sift4G	Benign	0.60	T
Polyphen		0.89	P
Vest4		0.74
MutPred		0.51		Gain of phosphorylation at T150 (P = 0.0994)
MVP		0.94
MPC		0.40
ClinPred		0.96	D
GERP RS		5.0
Varity_R		0.34
gMVP		0.30
Mutation Taster		=66/34	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: rs199973343; hg19: chr6-100390951;