rs812936

chr19-5844638-G-Achr19-5844638-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382749.2(FUT3):c.202C>T(p.Arg68Trp) variant causes a missense change. The variant allele was found at a frequency of 0.83 in 1,594,038 control chromosomes in the GnomAD database, including 546,177 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.84 (51983 hom., cov: 21)
  • Exomes 𝑓: 0.83 (494194 hom.)
• Consequence: FUT3 NM_001382749.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.04

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.923837E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FUT3	NM_001382749.2	c.202C>T	p.Arg68Trp	missense_variant	3/3
FUT3	NM_001097639.3	c.202C>T	p.Trp68=	synonymous_variant	3/3	ENST00000709635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FUT3	ENST00000303225.12	c.202C>T	p.Arg68Trp	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes AF: 0.837 AC: 123810 AN: 147952 Hom.: 51915 Cov.: 21

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.947

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.970

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.791

GnomAD3 exomes AF: 0.830 AC: 208584 AN: 251236 Hom.: 87155 AF XY: 0.824 AC XY: 111937 AN XY: 135826

Gnomad AFR exome AF: 0.883

Gnomad AMR exome AF: 0.895

Gnomad ASJ exome AF: 0.753

Gnomad EAS exome AF: 0.972

Gnomad SAS exome AF: 0.823

Gnomad FIN exome AF: 0.791

Gnomad NFE exome AF: 0.798

Gnomad OTH exome AF: 0.806

GnomAD4 exome AF: 0.830 AC: 1199882 AN: 1445968 Hom.: 494194 Cov.: 52 AF XY: 0.828 AC XY: 595474 AN XY: 719432

Gnomad4 AFR exome AF: 0.890

Gnomad4 AMR exome AF: 0.893

Gnomad4 ASJ exome AF: 0.770

Gnomad4 EAS exome AF: 0.982

Gnomad4 SAS exome AF: 0.819

Gnomad4 FIN exome AF: 0.807

Gnomad4 NFE exome AF: 0.823

Gnomad4 OTH exome AF: 0.835

GnomAD4 genome AF: 0.837 AC: 123937 AN: 148070 Hom.: 51983 Cov.: 21 AF XY: 0.835 AC XY: 60161 AN XY: 72034

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.851

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.970

Gnomad4 SAS AF: 0.831

Gnomad4 FIN AF: 0.801

Gnomad4 NFE AF: 0.806

Gnomad4 OTH AF: 0.795

Alfa AF: 0.812 Hom.: 98362

Bravo AF: 0.845

TwinsUK AF: 0.822 AC: 3049

ALSPAC AF: 0.821 AC: 3166

ESP6500AA AF: 0.887 AC: 3910

ESP6500EA AF: 0.800 AC: 6880

ExAC AF: 0.828 AC: 100468

Asia WGS AF: 0.921 AC: 3198 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.017
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	14
Dann	Benign	0.60
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.019	N
MetaRNN	Benign	0.0000029	T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	14	N;N;.;.;.;.
REVEL	Benign	0.070
Sift	Benign	1.0	T;T;.;.;.;.
Sift4G	Benign	1.0	T;T;T;T;T;T
Vest4		0.064
MPC		0.57
ClinPred		0.0037	T
GERP RS		2.3
gMVP		0.91

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

LitVar

Other links and lift over

dbSNP: rs812936; hg19: chr19-5844649; COSMIC: COSV54606175; COSMIC: COSV54606175;