rs562279593

Variant summary

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

The NM_003950.4(F2RL3):​c.557C>A​(p.Ala186Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,597,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. A186G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

F2RL3
NM_003950.4 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00500
Variant links:
Genes affected
F2RL3 (HGNC:3540): (F2R like thrombin or trypsin receptor 3) This gene encodes a member of the protease-activated receptor subfamily, part of the G-protein coupled receptor 1 family of proteins. The encoded receptor is proteolytically processed to reveal an extracellular N-terminal tethered ligand that binds to and activates the receptor. This receptor plays a role in blood coagulation, inflammation and response to pain. Hypomethylation at this gene may be associated with lung cancer in human patients. [provided by RefSeq, Sep 2016]

Genome browser will be placed here

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=0.08375338).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
F2RL3NM_003950.4 linkc.557C>A p.Ala186Asp missense_variant Exon 2 of 2 ENST00000248076.4 NP_003941.2 Q96RI0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
F2RL3ENST00000248076.4 linkc.557C>A p.Ala186Asp missense_variant Exon 2 of 2 1 NM_003950.4 ENSP00000248076.2 Q96RI0
F2RL3ENST00000599210.1 linkc.*211C>A 3_prime_UTR_variant Exon 2 of 2 2 ENSP00000471518.1 M0R0Y0

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152210
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000413
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000277
AC:
6
AN:
216356
Hom.:
0
AF XY:
0.0000249
AC XY:
3
AN XY:
120604
show subpopulations
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 SAS exome
AF:
0.000168
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000183
GnomAD4 exome
AF:
0.0000104
AC:
15
AN:
1445206
Hom.:
0
Cov.:
33
AF XY:
0.0000139
AC XY:
10
AN XY:
719010
show subpopulations
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:
0.000163
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152326
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000342
AC:
4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.15
T
Eigen
Benign
-0.50
Eigen_PC
Benign
-0.53
FATHMM_MKL
Benign
0.63
D
LIST_S2
Benign
0.58
T
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.084
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
L
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-1.7
N
REVEL
Benign
0.13
Sift
Benign
0.11
T
Sift4G
Benign
0.60
T
Polyphen
0.32
B
Vest4
0.15
MutPred
0.59
Loss of MoRF binding (P = 0.0358);
MVP
0.53
MPC
0.37
ClinPred
0.27
T
GERP RS
4.2
Varity_R
0.33
gMVP
0.36

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.

Other links and lift over

dbSNP: rs562279593; hg19: chr19-17000831; API