rs133073

Variant names:

• chr22-40679691-C-A
• NM_005297.4:c.39C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-40679691-C-A
• chr22-40679691-C-T

Variant summary

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

The NM_005297.4(MCHR1):​c.39C>A​(p.Asn13Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MCHR1 NM_005297.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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.39C>A	p.Asn13Lys	missense_variant	Exon 1 of 2	ENST00000249016.5	NP_005288.4
LOC124905123	XR_007068109.1	n.4323+917G>T		intron_variant	Intron 1 of 1
LOC124905123	XR_007068110.1	n.358+917G>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCHR1	ENST00000249016.5	c.39C>A	p.Asn13Lys	missense_variant	Exon 1 of 2	1	NM_005297.4	ENSP00000249016.5
MCHR1	ENST00000381433.3	c.39C>A	p.Asn13Lys	missense_variant	Exon 1 of 3	1		ENSP00000370841.3
MCHR1	ENST00000498400.1	n.132+287C>A		intron_variant	Intron 1 of 1	1
ENSG00000289292	ENST00000688408.2	n.367+917G>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 65 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	3.0
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.75	T;T
M_CAP	Uncertain	0.27	D
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.55	N;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.18
Sift	Uncertain	0.020	D;D
Sift4G	Benign	0.066	T;T
Polyphen		1.0	D;.
Vest4		0.52
MutPred		0.42		Gain of ubiquitination at N82 (P = 0.0025);Gain of ubiquitination at N82 (P = 0.0025);
MVP		0.81
MPC		0.40
ClinPred		0.93	D
GERP RS		0.41
Varity_R		0.088
gMVP		0.68

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: chr22-41075695;