chr22-40679729-C-A

Variant names:

• chr22-40679729-C-A
• rs142851281
• NM_005297.4:c.77C>A

Variant summary

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

The NM_005297.4(MCHR1):​c.77C>A​(p.Ser26*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,862 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.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MCHR1 NM_005297.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.788

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

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 rank	MANE	Protein	UniProt
MCHR1	NM_005297.4	c.77C>A	p.Ser26*	stop_gained	Exon 1 of 2	ENST00000249016.5	NP_005288.4
LOC124905123	XR_007068109.1	n.4323+879G>T		intron_variant	Intron 1 of 1
LOC124905123	XR_007068110.1	n.358+879G>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCHR1	ENST00000249016.5	c.77C>A	p.Ser26*	stop_gained	Exon 1 of 2	1	NM_005297.4	ENSP00000249016.5
MCHR1	ENST00000381433.3	c.77C>A	p.Ser26*	stop_gained	Exon 1 of 3	1		ENSP00000370841.3
MCHR1	ENST00000498400.1	n.132+325C>A		intron_variant	Intron 1 of 1	1
ENSG00000289292	ENST00000688408.2	n.367+879G>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248608 Hom.: 0 AF XY: 0.00000742 AC XY: 1 AN XY: 134772

Gnomad AFR exome AF: 0.0000622

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461862 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	26
DANN	Benign	0.97
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.038	N
Vest4		0.79
GERP RS		-2.3

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

LitVar

Other links and lift over

dbSNP: rs142851281; hg19: chr22-41075733;