NM_005304.5:c.251C>T

Variant names:

• chr19-35359141-C-T
• rs764883825
• NM_005304.5:c.251C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_005304.5(FFAR3):​c.251C>T​(p.Pro84Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000824 in 1,602,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P84R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000080 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000083 (0 hom.)
• Consequence: FFAR3 NM_005304.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33
• Publications: 0 publications found

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]

ENSG00000288731 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.872

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005304.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FFAR3	NM_005304.5	MANE Select	c.251C>T	p.Pro84Leu	missense	Exon 2 of 2	NP_005295.1	A0A0K0PUW7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FFAR3	ENST00000327809.5	TSL:1 MANE Select	c.251C>T	p.Pro84Leu	missense	Exon 2 of 2	ENSP00000328230.3	O14843
	FFAR3	ENST00000594310.1	TSL:6	c.251C>T	p.Pro84Leu	missense	Exon 1 of 1	ENSP00000469522.1	O14843
	FFAR3	ENST00000965195.1		c.251C>T	p.Pro84Leu	missense	Exon 2 of 2	ENSP00000635254.1

Frequencies

GnomAD3 genomes AF: 0.0000796 AC: 12 AN: 150752 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000178

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000642 AC: 16 AN: 249252 AF XY: 0.0000890

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000142

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000827 AC: 120 AN: 1451416 Hom.: 0 Cov.: 34 AF XY: 0.0000927 AC XY: 67 AN XY: 722472

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33384

American (AMR) AF: 0.00 AC: 0 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26040

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5538

European-Non Finnish (NFE) AF: 0.000107 AC: 118 AN: 1102938

Other (OTH) AF: 0.0000333 AC: 2 AN: 60020

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000796 AC: 12 AN: 150752 Hom.: 0 Cov.: 30 AF XY: 0.0000952 AC XY: 7 AN XY: 73550

African (AFR) AF: 0.00 AC: 0 AN: 41170

American (AMR) AF: 0.00 AC: 0 AN: 15060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000178 AC: 12 AN: 67432

Other (OTH) AF: 0.00 AC: 0 AN: 2038

Alfa AF: 0.000253 Hom.: 0

ExAC AF: 0.0000907 AC: 11

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.41	T
PhyloP100		3.3
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-8.4	D
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.71
MVP		0.54
ClinPred		0.98	D
GERP RS		4.5
PromoterAI		-0.023	Neutral
Varity_R		0.79
gMVP		0.75
Mutation Taster		=65/35	polymorphism

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

Other links and lift over

dbSNP: rs764883825; hg19: chr19-35850043;