19-51745980-T-C

Position:

• chr19-51745980-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1 PM2 BP4_Strong

The NM_002029.4(FPR1):​c.1015A>G​(p.Thr339Ala) 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. 16/21 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: FPR1 NM_002029.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.16

Genes affected

FPR1 (HGNC:3826): (formyl peptide receptor 1) This gene encodes a G protein-coupled receptor of mammalian phagocytic cells that is a member of the G-protein coupled receptor 1 family. The protein mediates the response of phagocytic cells to invasion of the host by microorganisms and is important in host defense and inflammation.[provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM1: In a modified_residue Phosphothreonine (size 0) in uniprot entity FPR1_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031758755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FPR1	NM_002029.4	c.1015A>G	p.Thr339Ala	missense_variant	2/2	ENST00000304748.5	NP_002020.1
FPR1	NM_001193306.2	c.1015A>G	p.Thr339Ala	missense_variant	3/3		NP_001180235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FPR1	ENST00000304748.5	c.1015A>G	p.Thr339Ala	missense_variant	2/2	1	NM_002029.4	ENSP00000302707.3
FPR1	ENST00000594900.2	c.1015A>G	p.Thr339Ala	missense_variant	3/3	4		ENSP00000470750.2
FPR1	ENST00000595042.5	c.1015A>G	p.Thr339Ala	missense_variant	3/3	2		ENSP00000471493.1
FPR1	ENST00000600815.2	c.1015A>G	p.Thr339Ala	missense_variant	2/2	3		ENSP00000472936.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 70

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Gingival disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 02, 2023

This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 339 of the FPR1 protein (p.Thr339Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FPR1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.0040
DANN	Benign	0.18
DEOGEN2	Benign	0.063	T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0022	N
LIST_S2	Benign	0.17	.;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.032	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.21	N;N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.19	.;N
REVEL	Benign	0.033
Sift	Benign	1.0	.;T
Sift4G	Benign	0.81	T;T
Polyphen		0.0010	B;B
Vest4		0.048
MutPred		0.10		Loss of glycosylation at T339 (P = 0.0488);Loss of glycosylation at T339 (P = 0.0488);
MVP		0.38
MPC		0.30
ClinPred		0.031	T
GERP RS		-6.5
Varity_R		0.020
gMVP		0.10

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: chr19-52249233;