chr10-93567118-G-T

Variant names:

• chr10-93567118-G-T
• rs749304646
• NM_001195755.2:c.398G>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001195755.2(FFAR4):​c.398G>T​(p.Ser133Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000261 in 1,456,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: FFAR4 NM_001195755.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.13

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.97

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FFAR4	NM_001195755.2	c.398G>T	p.Ser133Ile	missense_variant	Exon 1 of 3	ENST00000371481.9	NP_001182684.1
FFAR4	NM_181745.4	c.398G>T	p.Ser133Ile	missense_variant	Exon 1 of 4		NP_859529.2
FFAR4	XM_011539746.4	c.398G>T	p.Ser133Ile	missense_variant	Exon 1 of 3		XP_011538048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FFAR4	ENST00000371481.9	c.398G>T	p.Ser133Ile	missense_variant	Exon 1 of 3	1	NM_001195755.2	ENSP00000360536.5
FFAR4	ENST00000371483.8	c.398G>T	p.Ser133Ile	missense_variant	Exon 1 of 4	1		ENSP00000360538.4
FFAR4	ENST00000604414.1	c.398G>T	p.Ser133Ile	missense_variant	Exon 1 of 3	3		ENSP00000474477.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000261 AC: 38 AN: 1456322 Hom.: 0 Cov.: 33 AF XY: 0.0000235 AC XY: 17 AN XY: 724478

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000342

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	.;D;.
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Pathogenic	0.72	D
MetaRNN	Pathogenic	0.97	D;D;D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Pathogenic	4.0	H;H;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.3	D;D;.
REVEL	Pathogenic	0.83
Sift	Uncertain	0.0020	D;D;.
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.94
MutPred		0.78		Gain of stability (P = 0.0061);Gain of stability (P = 0.0061);Gain of stability (P = 0.0061);
MVP		0.97
MPC		1.6
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.99
gMVP		0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs749304646; hg19: chr10-95326875;