NM_005297.4:c.-63C>A

Variant names:

• chr22-40679590-C-A
• rs770409636
• NM_005297.4:c.-63C>A

Variant summary

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

The NM_005297.4(MCHR1):​c.-63C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MCHR1 NM_005297.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 0 publications found

Genes affected

MCHR1 (HGNC:4479): (melanin concentrating hormone receptor 1) The protein encoded by this gene, a member of the G protein-coupled receptor family 1, is an integral plasma membrane protein which binds melanin-concentrating hormone. The encoded protein can inhibit cAMP accumulation and stimulate intracellular calcium flux, and is probably involved in the neuronal regulation of food consumption. Although structurally similar to somatostatin receptors, this protein does not seem to bind somatostatin. [provided by RefSeq, Jul 2008]

ENSG00000289292 (HGNC:):

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=0.26215416).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005297.4. 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
	MCHR1	NM_005297.4	MANE Select	c.-63C>A		5_prime_UTR	Exon 1 of 2	NP_005288.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCHR1	ENST00000249016.5	TSL:1 MANE Select	c.-63C>A		5_prime_UTR	Exon 1 of 2	ENSP00000249016.5	Q99705
	MCHR1	ENST00000381433.3	TSL:1	c.-63C>A		5_prime_UTR	Exon 1 of 3	ENSP00000370841.3	A6ZJ87
	MCHR1	ENST00000498400.1	TSL:1	n.132+186C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461556 Hom.: 0 Cov.: 65 AF XY: 0.00000138 AC XY: 1 AN XY: 727108

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111866

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.067	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.50	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.2
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.19
Sift	Benign	0.044	D
Sift4G	Benign	0.25	T
Polyphen		0.92	P
Vest4		0.32
MutPred		0.39		Gain of catalytic residue at Q49 (P = 0.0048)
MVP		0.78
MPC		0.16
ClinPred		0.55	D
GERP RS		5.0
PromoterAI		-0.020	Neutral
Varity_R		0.25
gMVP		0.37

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: rs770409636; hg19: chr22-41075594;