19-35352329-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005303.3(FFAR1):c.778C>G(p.Leu260Val) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FFAR1 NM_005303.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.727

Genes affected

FFAR1 (HGNC:4498): (free fatty acid receptor 1) 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 medium and long chain free fatty acids and may be involved in the metabolic regulation of insulin secretion. Polymorphisms in this gene may be associated with type 2 diabetes. [provided by RefSeq, Apr 2009]

ACMG classification

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=0.218548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FFAR1	NM_005303.3	c.778C>G	p.Leu260Val	missense_variant	2/2	ENST00000246553.4
FFAR1	XM_047438698.1	c.778C>G	p.Leu260Val	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FFAR1	ENST00000246553.4	c.778C>G	p.Leu260Val	missense_variant	2/2		NM_005303.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 09, 2021

The c.778C>G (p.L260V) alteration is located in exon 1 (coding exon 1) of the FFAR1 gene. This alteration results from a C to G substitution at nucleotide position 778, causing the leucine (L) at amino acid position 260 to be replaced by a valine (V). 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	0.10
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	15
Dann	Uncertain	0.99
DEOGEN2	Benign	0.088	T
Eigen	Benign	0.079
Eigen_PC	Benign	0.047
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	0.95	N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.18
Sift	Benign	0.54	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.18
MutPred		0.59		Gain of methylation at K259 (P = 0.0404);
MVP		0.59
MPC		0.85
ClinPred		0.34	T
GERP RS		2.1
Varity_R		0.046
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr19-35843232;