chr19-5844099-G-T

Variant names:

• chr19-5844099-G-T
• ENST00000303225.12:c.741C>A

Variant summary

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

The NM_000149.4(FUT3):​c.741C>A​(p.Phe247Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,700 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FUT3 NM_000149.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

Genes affected

FUT3 (HGNC:4014): (fucosyltransferase 3 (Lewis blood group)) The Lewis histo-blood group system comprises a set of fucosylated glycosphingolipids that are synthesized by exocrine epithelial cells and circulate in body fluids. The glycosphingolipids function in embryogenesis, tissue differentiation, tumor metastasis, inflammation, and bacterial adhesion. They are secondarily absorbed to red blood cells giving rise to their Lewis phenotype. This gene is a member of the fucosyltransferase family, which catalyzes the addition of fucose to precursor polysaccharides in the last step of Lewis antigen biosynthesis. It encodes an enzyme with alpha(1,3)-fucosyltransferase and alpha(1,4)-fucosyltransferase activities. Mutations in this gene are responsible for the majority of Lewis antigen-negative phenotypes. Differences in the expression of this gene are associated with host susceptibility to viral infection. [provided by RefSeq, Aug 2020]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT3	NM_000149.4	c.741C>A	p.Phe247Leu	missense_variant	Exon 3 of 3		NP_000140.1
FUT3	NM_001097639.3	c.741C>A	p.Phe247Leu	missense_variant	Exon 3 of 3		NP_001091108.3
FUT3	NM_001097640.3	c.741C>A	p.Phe247Leu	missense_variant	Exon 3 of 3		NP_001091109.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUT3	ENST00000303225.12	c.741C>A	p.Phe247Leu	missense_variant	Exon 3 of 3	1		ENSP00000305603.5
FUT3	ENST00000458379.7	c.741C>A	p.Phe247Leu	missense_variant	Exon 2 of 2	1		ENSP00000416443.1
FUT3	ENST00000589620.6	c.741C>A	p.Phe247Leu	missense_variant	Exon 3 of 3	1		ENSP00000465804.1
FUT3	ENST00000589918.5	c.741C>A	p.Phe247Leu	missense_variant	Exon 3 of 3	1		ENSP00000468123.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461700 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727158

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	12
DANN	Uncertain	0.99
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.087	N
M_CAP	Benign	0.0066	T
MetaRNN	Uncertain	0.74	D;D;D;D
MetaSVM	Benign	-0.78	T
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-5.1	D;D;.;.
REVEL	Benign	0.21
Sift	Benign	0.056	T;T;.;.
Sift4G	Benign	0.074	T;T;T;T
Vest4		0.35
MutPred		0.89		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP		0.32
MPC		1.6
ClinPred		0.99	D
GERP RS		-0.21
gMVP		0.47

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-5844110;