Variant 19-16889875-C-T 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_003950.4(F2RL3):c.412C>T(p.Arg138Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000326 in 1,589,536 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 0.00042 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

F2RL3
NM_003950.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.577

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]

F2RL3 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=0.23306671).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F2RL3	NM_003950.4 linkuse as main transcript	c.412C>T	p.Arg138Cys	missense_variant	2/2	ENST00000248076.4	NP_003941.2	Q96RI0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F2RL3	ENST00000248076.4 linkuse as main transcript	c.412C>T	p.Arg138Cys	missense_variant	2/2	1	NM_003950.4	ENSP00000248076.2		Q96RI0
F2RL3	ENST00000599210.1 linkuse as main transcript	c.*66C>T		3_prime_UTR_variant	2/2	2		ENSP00000471518.1		M0R0Y0

Frequencies

GnomAD3 genomes

AF:

0.000421

AC:

AN:

151924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000580

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000545

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000243

AC:

AN:

202010

Hom.:

AF XY:

0.000293

AC XY:

AN XY:

112596

show subpopulations

Gnomad AFR exome

AF:

0.000405

Gnomad AMR exome

AF:

0.000222

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000351

Gnomad FIN exome

AF:

0.0000912

Gnomad NFE exome

AF:

0.000362

Gnomad OTH exome

AF:

0.000581

GnomAD4 exome

AF:

0.000316

AC:

454

AN:

1437492

Hom.:

Cov.:

AF XY:

0.000330

AC XY:

236

AN XY:

714746

show subpopulations

Gnomad4 AFR exome

AF:

0.000451

Gnomad4 AMR exome

AF:

0.000257

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000236

Gnomad4 FIN exome

AF:

0.0000996

Gnomad4 NFE exome

AF:

0.000363

Gnomad4 OTH exome

AF:

0.000336

GnomAD4 genome

AF:

0.000421

AC:

AN:

152044

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.000579

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000545

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000410

Hom.:

Bravo

AF:

0.000431

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000471

AC:

ESP6500EA

AF:

0.000241

AC:

ExAC

AF:

0.000281

AC:

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

Aug 02, 2021

The c.412C>T (p.R138C) alteration is located in exon 2 (coding exon 2) of the F2RL3 gene. This alteration results from a C to T substitution at nucleotide position 412, causing the arginine (R) at amino acid position 138 to be replaced by a cysteine (C). 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

0.17

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.68

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.26

Sift

Benign

0.055

Sift4G

Benign

0.18

Polyphen

0.99

Vest4

0.26

MVP

0.80

MPC

0.58

ClinPred

0.051

GERP RS

-2.3

Varity_R

0.17

gMVP

0.21

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