12-108291935-C-T

Variant names:

• chr12-108291935-C-T
• rs777870525
• NM_001142343.2:c.1028G>A

Variant summary

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

The NM_001142343.2(CMKLR1):​c.1028G>A​(p.Gly343Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. G343V) 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: 1.35
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08940509).

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.1028G>A	p.Gly343Asp	missense	Exon 4 of 4	NP_001135815.1	Q99788-1
	CMKLR1	NM_001142344.2		c.1028G>A	p.Gly343Asp	missense	Exon 3 of 3	NP_001135816.1	Q99788-1
	CMKLR1	NM_001142345.2		c.1028G>A	p.Gly343Asp	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.1028G>A	p.Gly343Asp	missense	Exon 4 of 4	ENSP00000449716.1	Q99788-1
	CMKLR1	ENST00000552995.5	TSL:1	c.1022G>A	p.Gly341Asp	missense	Exon 3 of 3	ENSP00000447579.1	Q99788-2
	CMKLR1	ENST00000312143.11	TSL:2	c.1028G>A	p.Gly343Asp	missense	Exon 3 of 3	ENSP00000311733.7	Q99788-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.54
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.4
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.042
Sift	Benign	0.35	T
Sift4G	Benign	0.25	T
Polyphen		0.44	B
Vest4		0.20
MutPred		0.29		Gain of catalytic residue at H344 (P = 0.0058)
MVP		0.53
MPC		0.30
ClinPred		0.11	T
GERP RS		2.4
Varity_R		0.034
gMVP		0.29
Mutation Taster		=91/9	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: rs777870525; hg19: chr12-108685712; COSMIC: COSV56441652; COSMIC: COSV56441652;