19-51824661-A-T

Position:

• chr19-51824661-A-T

Variant summary

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

The NM_002030.5(FPR3):​c.913A>T​(p.Met305Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FPR3 NM_002030.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.194

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=0.09668821).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FPR3	NM_002030.5	c.913A>T	p.Met305Leu	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.913A>T	p.Met305Leu	missense_variant	2/2	1	NM_002030.5	ENSP00000341821.3
FPR3	ENST00000595991.1	c.913A>T	p.Met305Leu	missense_variant	2/2	4		ENSP00000470471.1
ZNF577	ENST00000638827.1	n.*600-12987T>A		intron_variant		5		ENSP00000492704.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461858 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

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

Aug 07, 2024

The c.913A>T (p.M305L) alteration is located in exon 2 (coding exon 1) of the FPR3 gene. This alteration results from a A to T substitution at nucleotide position 913, causing the methionine (M) at amino acid position 305 to be replaced by a leucine (L). 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	0.16
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.029
DANN	Benign	0.31
DEOGEN2	Benign	0.027	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.34	.;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.097	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.69	N;.
REVEL	Benign	0.021
Sift	Benign	0.52	T;.
Sift4G	Benign	0.47	T;T
Polyphen		0.0	B;B
Vest4		0.18
MutPred		0.41		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.095
MPC		0.25
ClinPred		0.060	T
GERP RS		-4.7
Varity_R		0.051
gMVP		0.26

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: chr19-52327914;