NM_001370087.1:c.301G>C

Variant names:

• chr19-35450015-G-C
• NM_001370087.1:c.301G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001370087.1(FFAR2):​c.301G>C​(p.Ala101Pro) 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 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. A101E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FFAR2 NM_001370087.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.70
• Publications: 0 publications found

Genes affected

FFAR2 (HGNC:4501): (free fatty acid receptor 2) This gene encodes a member of the GP40 family of G protein-coupled receptors that are clustered together on chromosome 19. The encoded protein is a receptor for short chain free fatty acids and may be involved in the inflammatory response and in regulating lipid plasma levels. [provided by RefSeq, Apr 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.914

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370087.1. 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
	FFAR2	NM_001370087.1	MANE Select	c.301G>C	p.Ala101Pro	missense	Exon 2 of 2	NP_001357016.1	C6KYL4
	FFAR2	NM_005306.3		c.301G>C	p.Ala101Pro	missense	Exon 3 of 3	NP_005297.1	C6KYL4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FFAR2	ENST00000599180.3	TSL:1 MANE Select	c.301G>C	p.Ala101Pro	missense	Exon 2 of 2	ENSP00000473159.1	O15552
	FFAR2	ENST00000246549.2	TSL:6	c.301G>C	p.Ala101Pro	missense	Exon 1 of 1	ENSP00000246549.2	O15552
	FFAR2	ENST00000601590.1	TSL:5	n.17-1138G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.057	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		2.7
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.9	N
REVEL	Pathogenic	0.68
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.81		Loss of glycosylation at S104 (P = 0.1553)
MVP		0.93
MPC		0.86
ClinPred		0.96	D
GERP RS		5.7
PromoterAI		0.0052	Neutral
Varity_R		0.95
gMVP		0.85
Mutation Taster		=55/45	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

hg19: chr19-35940917;