chr10-93576121-A-C

Variant names:

• chr10-93576121-A-C
• rs777339849
• NM_001195755.2:c.598A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001195755.2(FFAR4):​c.598A>C​(p.Thr200Pro) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T200S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FFAR4 NM_001195755.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.25
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16424823).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195755.2. 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
	FFAR4	NM_001195755.2	MANE Select	c.598A>C	p.Thr200Pro	missense	Exon 2 of 3	NP_001182684.1	Q5NUL3-2
	FFAR4	NM_181745.4		c.598A>C	p.Thr200Pro	missense	Exon 2 of 4	NP_859529.2	Q5NUL3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FFAR4	ENST00000371481.9	TSL:1 MANE Select	c.598A>C	p.Thr200Pro	missense	Exon 2 of 3	ENSP00000360536.5	Q5NUL3-2
	FFAR4	ENST00000371483.8	TSL:1	c.598A>C	p.Thr200Pro	missense	Exon 2 of 4	ENSP00000360538.4	Q5NUL3-1
	FFAR4	ENST00000604414.1	TSL:3	c.598A>C	p.Thr200Pro	missense	Exon 2 of 3	ENSP00000474477.1	S4R3L2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.046
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N
PhyloP100		3.2
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.031
Sift	Benign	0.17	T
Sift4G	Benign	0.21	T
Polyphen		0.34	B
Vest4		0.20
MutPred		0.43		Loss of glycosylation at T200 (P = 0.0577)
MVP		0.65
MPC		0.92
ClinPred		0.48	T
GERP RS		4.0
Varity_R		0.25
gMVP		0.62
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs777339849; hg19: chr10-95335878;