Genetic Variant FFAR3:p.Ala49Thr (chr19-35359035-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005304.5(FFAR3):c.145G>A(p.Ala49Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000441 in 1,611,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

FFAR3
NM_005304.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.89

Variant links:

Genes affected

FFAR3 (HGNC:4499): (free fatty acid receptor 3) Enables G protein-coupled receptor activity. Involved in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway and cellular response to fatty acid. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

FFAR3 links:

Genome browser will be placed here

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=0.072282076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FFAR3	NM_005304.5 link	c.145G>A	p.Ala49Thr	missense_variant	Exon 2 of 2	ENST00000327809.5	NP_005295.1
FFAR3	XM_011526858.3 link	c.256G>A	p.Ala86Thr	missense_variant	Exon 2 of 2		XP_011525160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FFAR3	ENST00000327809.5 link	c.145G>A	p.Ala49Thr	missense_variant	Exon 2 of 2	1	NM_005304.5	ENSP00000328230.3		O14843
FFAR3	ENST00000594310.1 link	c.145G>A	p.Ala49Thr	missense_variant	Exon 1 of 1	6		ENSP00000469522.1		O14843

Frequencies

GnomAD3 genomes

AF:

0.000277

AC:

AN:

151638

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000920

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000757

AC:

AN:

251138

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1459974

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726316

show subpopulations

Gnomad4 AFR exome

AF:

0.000628

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000277

AC:

AN:

151756

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

74180

show subpopulations

Gnomad4 AFR

AF:

0.000942

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000144

Hom.:

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000989

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.145G>A (p.A49T) alteration is located in exon 2 (coding exon 1) of the FFAR3 gene. This alteration results from a G to A substitution at nucleotide position 145, causing the alanine (A) at amino acid position 49 to be replaced by a threonine (T). 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

0.20

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.39

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.058

T;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.79

.;T

M_CAP

Benign

0.0093

MetaRNN

Benign

0.072

T;T

MetaSVM

Benign

-0.81

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.33

N;.

REVEL

Benign

0.14

Sift

Uncertain

0.0080

D;.

Sift4G

Benign

0.30

T;T

Polyphen

0.97

D;D

Vest4

0.16

MVP

0.31

ClinPred

0.13

GERP RS

5.0

Varity_R

0.17

gMVP

0.31

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