Variant 12-108291902-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001142343.2(CMKLR1):c.1061C>T(p.Thr354Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CMKLR1
NM_001142343.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.50

Variant links:

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]

CMKLR1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25150058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMKLR1	NM_001142343.2 linkuse as main transcript	c.1061C>T	p.Thr354Ile	missense_variant	4/4	ENST00000550402.6	NP_001135815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMKLR1	ENST00000550402.6 linkuse as main transcript	c.1061C>T	p.Thr354Ile	missense_variant	4/4	1	NM_001142343.2	ENSP00000449716	A1	Q99788-1
CMKLR1	ENST00000552995.5 linkuse as main transcript	c.1055C>T	p.Thr352Ile	missense_variant	3/3	1		ENSP00000447579	P4	Q99788-2
CMKLR1	ENST00000312143.11 linkuse as main transcript	c.1061C>T	p.Thr354Ile	missense_variant	3/3	2		ENSP00000311733	A1	Q99788-1
CMKLR1	ENST00000412676.5 linkuse as main transcript	c.1061C>T	p.Thr354Ile	missense_variant	3/3	3		ENSP00000401293	A1	Q99788-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2022

The c.1061C>T (p.T354I) alteration is located in exon 4 (coding exon 2) of the CMKLR1 gene. This alteration results from a C to T substitution at nucleotide position 1061, causing the threonine (T) at amino acid position 354 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

0.0039

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;T;.;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

T;.;T;.

M_CAP

Benign

0.069

MetaRNN

Benign

0.25

T;T;T;T

MetaSVM

Benign

-0.31

MutationAssessor

Uncertain

2.1

M;M;.;M

MutationTaster

Benign

0.63

D;D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.2

N;N;N;N

REVEL

Benign

0.22

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Uncertain

0.0070

D;D;D;D

Polyphen

1.0

D;D;.;D

Vest4

0.17

MutPred

0.33

Gain of catalytic residue at M359 (P = 0.0026);Gain of catalytic residue at M359 (P = 0.0026);.;Gain of catalytic residue at M359 (P = 0.0026);

MVP

0.91

MPC

0.65

ClinPred

0.90

GERP RS

5.4

Varity_R

0.14

gMVP

0.38

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over