12-108292476-T-A

Variant names:

• chr12-108292476-T-A
• rs780132798
• NM_001142343.2:c.487A>T

Variant summary

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

The NM_001142343.2(CMKLR1):​c.487A>T​(p.Ile163Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I163L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CMKLR1 NM_001142343.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96
• Publications: 0 publications found

Genes affected

CMKLR1 (HGNC:2121): (chemerin chemokine-like receptor 1) Enables adipokinetic hormone binding activity and adipokinetic hormone receptor activity. Involved in several processes, including negative regulation of NF-kappaB transcription factor activity; positive regulation of macrophage chemotaxis; and regulation of calcium-mediated signaling. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142343.2. 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
	CMKLR1	NM_001142343.2	MANE Select	c.487A>T	p.Ile163Phe	missense	Exon 4 of 4	NP_001135815.1	Q99788-1
	CMKLR1	NM_001142344.2		c.487A>T	p.Ile163Phe	missense	Exon 3 of 3	NP_001135816.1	Q99788-1
	CMKLR1	NM_001142345.2		c.487A>T	p.Ile163Phe	missense	Exon 3 of 3	NP_001135817.1	Q99788-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMKLR1	ENST00000550402.6	TSL:1 MANE Select	c.487A>T	p.Ile163Phe	missense	Exon 4 of 4	ENSP00000449716.1	Q99788-1
	CMKLR1	ENST00000552995.5	TSL:1	c.481A>T	p.Ile161Phe	missense	Exon 3 of 3	ENSP00000447579.1	Q99788-2
	CMKLR1	ENST00000312143.11	TSL:2	c.487A>T	p.Ile163Phe	missense	Exon 3 of 3	ENSP00000311733.7	Q99788-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	0.13
Eigen_PC	Benign	-0.023
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.091	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Pathogenic	3.8	H
PhyloP100		3.0
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.015	D
Polyphen		0.92	P
Vest4		0.48
MutPred		0.48		Gain of catalytic residue at M158 (P = 0)
MVP		0.97
MPC		0.75
ClinPred		0.97	D
GERP RS		3.0
Varity_R		0.27
gMVP		0.69
Mutation Taster		=83/17	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: rs780132798; hg19: chr12-108686253;