Genetic Variant FFAR3:p.Val152Ile (chr19-35359344-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_005304.5(FFAR3):c.454G>A(p.Val152Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000276 in 152,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FFAR3
NM_005304.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.956

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0071778).

BP6

Variant 19-35359344-G-A is Benign according to our data. Variant chr19-35359344-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2345045.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FFAR3	NM_005304.5 link	c.454G>A	p.Val152Ile	missense_variant	Exon 2 of 2	ENST00000327809.5	NP_005295.1
FFAR3	XM_011526858.3 link	c.565G>A	p.Val189Ile	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.454G>A	p.Val152Ile	missense_variant	Exon 2 of 2	1	NM_005304.5	ENSP00000328230.3		O14843
FFAR3	ENST00000594310.1 link	c.454G>A	p.Val152Ile	missense_variant	Exon 1 of 1	6		ENSP00000469522.1		O14843

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000292

AC:

AN:

246762

Hom.:

AF XY:

0.000352

AC XY:

AN XY:

133650

show subpopulations

Gnomad AFR exome

AF:

0.000443

Gnomad AMR exome

AF:

0.0000583

Gnomad ASJ exome

AF:

0.00333

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000428

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000144

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000210

AC:

307

AN:

1460072

Hom.:

Cov.:

AF XY:

0.000235

AC XY:

171

AN XY:

726320

show subpopulations

Gnomad4 AFR exome

AF:

0.000628

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00368

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000592

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000981

Gnomad4 OTH exome

AF:

0.000332

GnomAD4 genome

AF:

0.000276

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.000555

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000576

Hom.:

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000222

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 18, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.016

DANN

Benign

0.18

DEOGEN2

Benign

0.031

T;T

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.63

.;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.0072

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

0.26

N;.

REVEL

Benign

0.033

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.0070

B;B

Vest4

0.061

MVP

0.076

ClinPred

0.0027

GERP RS

-11

Varity_R

0.025

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

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