19-51824418-A-G

Position:

• chr19-51824418-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002030.5(FPR3):​c.670A>G​(p.Ile224Val) 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. 14/21 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)
• Consequence: FPR3 NM_002030.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70

Genes affected

FPR3 (HGNC:3828): (formyl peptide receptor 3) Predicted to enable N-formyl peptide receptor activity and complement receptor activity. Predicted to be involved in several processes, including complement receptor mediated signaling pathway; phospholipase C-activating G protein-coupled receptor signaling pathway; and positive regulation of cytosolic calcium ion concentration. Predicted to act upstream of or within G protein-coupled receptor signaling pathway. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ZNF577 (HGNC:28673): (zinc finger protein 577) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.21728525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FPR3	NM_002030.5	c.670A>G	p.Ile224Val	missense_variant	2/2	ENST00000339223.5	NP_002021.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FPR3	ENST00000339223.5	c.670A>G	p.Ile224Val	missense_variant	2/2	1	NM_002030.5	ENSP00000341821.3
FPR3	ENST00000595991.1	c.670A>G	p.Ile224Val	missense_variant	2/2	4		ENSP00000470471.1
ZNF577	ENST00000638827.1	n.*600-12744T>C		intron_variant		5		ENSP00000492704.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2024

The c.670A>G (p.I224V) alteration is located in exon 2 (coding exon 1) of the FPR3 gene. This alteration results from a A to G substitution at nucleotide position 670, causing the isoleucine (I) at amino acid position 224 to be replaced by a valine (V). 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	0.18
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.76	.;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.64	N;.
REVEL	Benign	0.092
Sift	Benign	0.094	T;.
Sift4G	Benign	0.17	T;T
Polyphen		0.58	P;P
Vest4		0.11
MutPred		0.58		Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.61
MPC		0.34
ClinPred		0.49	T
GERP RS		2.3
Varity_R		0.11
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-52327671;