19-51824665-G-A

Position:

• chr19-51824665-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_002030.5(FPR3):​c.917G>A​(p.Gly306Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 8.42

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.962

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FPR3	NM_002030.5	c.917G>A	p.Gly306Asp	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.917G>A	p.Gly306Asp	missense_variant	2/2	1	NM_002030.5	ENSP00000341821.3
FPR3	ENST00000595991.1	c.917G>A	p.Gly306Asp	missense_variant	2/2	4		ENSP00000470471.1
ZNF577	ENST00000638827.1	n.*600-12991C>T		intron_variant		5		ENSP00000492704.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

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

Jul 27, 2024

The c.917G>A (p.G306D) alteration is located in exon 2 (coding exon 1) of the FPR3 gene. This alteration results from a G to A substitution at nucleotide position 917, causing the glycine (G) at amino acid position 306 to be replaced by an aspartic acid (D). 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	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T
Eigen	Uncertain	0.35
Eigen_PC	Benign	0.089
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	.;D
M_CAP	Benign	0.0051	T
MetaRNN	Pathogenic	0.96	D;D
MetaSVM	Benign	-0.39	T
MutationAssessor	Pathogenic	3.7	H;H
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-6.6	D;.
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;D
Vest4		0.79
MutPred		0.76		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.65
MPC		1.1
ClinPred		0.96	D
GERP RS		2.3
Varity_R		0.60
gMVP		0.48

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

Other links and lift over

dbSNP: rs2084218723; hg19: chr19-52327918;