chr6-99943043-C-A

Variant names:

• chr6-99943043-C-A
• rs201607907
• NM_001040179.2:c.493G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001040179.2(MCHR2):​c.493G>T​(p.Ala165Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,612,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: MCHR2 NM_001040179.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.433
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14655489).

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.493G>T	p.Ala165Ser	missense	Exon 4 of 6	NP_001035269.1	Q969V1
	MCHR2	NM_032503.3		c.493G>T	p.Ala165Ser	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.493G>T	p.Ala165Ser	missense	Exon 4 of 6	ENSP00000281806.2	Q969V1
	MCHR2	ENST00000369212.2	TSL:1	c.493G>T	p.Ala165Ser	missense	Exon 4 of 6	ENSP00000358214.1	Q969V1
	MCHR2	ENST00000880237.1		c.493G>T	p.Ala165Ser	missense	Exon 4 of 6	ENSP00000550296.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152046 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000191

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000996 AC: 25 AN: 250898 AF XY: 0.000133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000212

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000162 AC: 237 AN: 1460942 Hom.: 0 Cov.: 30 AF XY: 0.000160 AC XY: 116 AN XY: 726772

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.000230 AC: 6 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.000204 AC: 227 AN: 1111382

Other (OTH) AF: 0.0000497 AC: 3 AN: 60342

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152046 Hom.: 0 Cov.: 31 AF XY: 0.0000943 AC XY: 7 AN XY: 74268

African (AFR) AF: 0.0000483 AC: 2 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

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

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 67996

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.000208 Hom.: 0

Bravo AF: 0.000121

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000577 AC: 7

EpiCase AF: 0.00

EpiControl AF: 0.000297

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	-0.40	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.098	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.33	N
PhyloP100		0.43
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.082
Sift	Benign	0.075	T
Sift4G	Benign	0.37	T
Polyphen		0.015	B
Vest4		0.39
MVP		0.54
MPC		0.079
ClinPred		0.086	T
GERP RS		4.0
Varity_R		0.17
gMVP		0.21
Mutation Taster		=92/8	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: rs201607907; hg19: chr6-100390919;