chr10-93579193-T-C

Position:

• chr10-93579193-T-C

Variant summary

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

The ENST00000371483.8(FFAR4):​c.731T>C​(p.Val244Ala) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FFAR4 ENST00000371483.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0570

Genes affected

FFAR4 (HGNC:19061): (free fatty acid receptor 4) This gene encodes a G protein-coupled receptor (GPR) which belongs to the rhodopsin family of GPRs. The encoded protein functions as a receptor for free fatty acids, including omega-3, and participates in suppressing anti-inflammatory responses and insulin sensitizing. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

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=0.06866422).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FFAR4	NM_001195755.2	c.696+2974T>C		intron_variant		ENST00000371481.9
FFAR4	NM_181745.4	c.731T>C	p.Val244Ala	missense_variant	3/4
FFAR4	XM_011539746.4	c.*149T>C		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FFAR4	ENST00000371483.8	c.731T>C	p.Val244Ala	missense_variant	3/4	1
FFAR4	ENST00000371481.9	c.696+2974T>C		intron_variant		1	NM_001195755.2	P1
FFAR4	ENST00000604414.1	c.696+2974T>C		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

May 04, 2023

The c.731T>C (p.V244A) alteration is located in exon 3 (coding exon 3) of the FFAR4 gene. This alteration results from a T to C substitution at nucleotide position 731, causing the valine (V) at amino acid position 244 to be replaced by an alanine (A). 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
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.0
DANN	Benign	0.80
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.65	N
REVEL	Benign	0.046
Sift	Benign	0.42	T
Sift4G	Benign	0.32	T
Polyphen		0.011	B
Vest4		0.21
MutPred		0.40		Gain of disorder (P = 0.0461);
MVP		0.37
MPC		0.63
ClinPred		0.057	T
GERP RS		2.3
Varity_R		0.027
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: chr10-95338950;