12-108291935-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001142343.2(CMKLR1):​c.1028G>T​(p.Gly343Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CMKLR1 NM_001142343.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06436059).

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>T	p.Gly343Val	missense	Exon 4 of 4	NP_001135815.1	Q99788-1
	CMKLR1	NM_001142344.2		c.1028G>T	p.Gly343Val	missense	Exon 3 of 3	NP_001135816.1	Q99788-1
	CMKLR1	NM_001142345.2		c.1028G>T	p.Gly343Val	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>T	p.Gly343Val	missense	Exon 4 of 4	ENSP00000449716.1	Q99788-1
	CMKLR1	ENST00000552995.5	TSL:1	c.1022G>T	p.Gly341Val	missense	Exon 3 of 3	ENSP00000447579.1	Q99788-2
	CMKLR1	ENST00000312143.11	TSL:2	c.1028G>T	p.Gly343Val	missense	Exon 3 of 3	ENSP00000311733.7	Q99788-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000802 AC: 2 AN: 249458 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461880 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.000140 Hom.: 0

ExAC AF: 0.00000827 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.66
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.50	N
PhyloP100		1.4
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.020
Sift	Benign	0.53	T
Sift4G	Benign	0.34	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.31		Gain of catalytic residue at G343 (P = 8e-04)
MVP		0.46
MPC		0.20
ClinPred		0.018	T
GERP RS		2.4
Varity_R		0.027
gMVP		0.35
Mutation Taster		=90/10	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;