chr22-40679591-A-C

Position:

• chr22-40679591-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005297.4(MCHR1):​c.-62A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MCHR1 NM_005297.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.27

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCHR1	NM_005297.4	c.-62A>C		5_prime_UTR_variant	1/2	ENST00000249016.5
LOC124905123	XR_007068110.1	n.358+1017T>G		intron_variant, non_coding_transcript_variant
LOC124905123	XR_007068109.1	n.4323+1017T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCHR1	ENST00000249016.5	c.-62A>C		5_prime_UTR_variant	1/2	1	NM_005297.4	P1
MCHR1	ENST00000381433.3	c.-62A>C		5_prime_UTR_variant	1/3	1
MCHR1	ENST00000498400.1	n.132+187A>C		intron_variant, non_coding_transcript_variant		1
	ENST00000688408.2	n.367+1017T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 02, 2023

The c.146A>C (p.Q49P) alteration is located in exon 1 (coding exon 1) of the MCHR1 gene. This alteration results from a A to C substitution at nucleotide position 146, causing the glutamine (Q) at amino acid position 49 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.067	T;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.47	T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.34	N;.
MutationTaster	Benign	0.52	D;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.31	N;N
REVEL	Uncertain	0.30
Sift	Uncertain	0.022	D;D
Sift4G	Benign	0.26	T;T
Polyphen		0.99	D;.
Vest4		0.44
MutPred		0.43		Gain of glycosylation at Q49 (P = 0.0072);Gain of glycosylation at Q49 (P = 0.0072);
MVP		0.80
MPC		0.16
ClinPred		0.50	D
GERP RS		5.0
Varity_R		0.23
gMVP		0.53

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-41075595;