19-5843773-A-T

Variant names:

• chr19-5843773-A-T
• rs3894326
• ENST00000303225.12:c.1067T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000303225.12(FUT3):​c.1067T>A​(p.Ile356Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0723 in 1,613,650 control chromosomes in the GnomAD database, including 4,924 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 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 0.065 (381 hom., cov: 32)
  • Exomes 𝑓: 0.073 (4543 hom.)
• Consequence: FUT3 ENST00000303225.12 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• Publications: 62 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016589463).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT3	NM_000149.4	c.1067T>A	p.Ile356Lys	missense_variant	Exon 3 of 3		NP_000140.1
FUT3	NM_001097639.3	c.1067T>A	p.Ile356Lys	missense_variant	Exon 3 of 3		NP_001091108.3
FUT3	NM_001097640.3	c.1067T>A	p.Ile356Lys	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.1067T>A	p.Ile356Lys	missense_variant	Exon 3 of 3	1		ENSP00000305603.5
FUT3	ENST00000458379.7	c.1067T>A	p.Ile356Lys	missense_variant	Exon 2 of 2	1		ENSP00000416443.1
FUT3	ENST00000589620.6	c.1067T>A	p.Ile356Lys	missense_variant	Exon 3 of 3	1		ENSP00000465804.1
FUT3	ENST00000589918.5	c.1067T>A	p.Ile356Lys	missense_variant	Exon 3 of 3	1		ENSP00000468123.1

Frequencies

GnomAD3 genomes AF: 0.0652 AC: 9923 AN: 152184 Hom.: 378 Cov.: 32

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.0407

Gnomad AMR AF: 0.0654

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0552

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0653

Gnomad OTH AF: 0.0840

GnomAD2 exomes AF: 0.0852 AC: 21414 AN: 251366 AF XY: 0.0919

Gnomad AFR exome AF: 0.0387

Gnomad AMR exome AF: 0.0488

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.134

Gnomad FIN exome AF: 0.0557

Gnomad NFE exome AF: 0.0706

Gnomad OTH exome AF: 0.0884

GnomAD4 exome AF: 0.0730 AC: 106716 AN: 1461346 Hom.: 4543 Cov.: 33 AF XY: 0.0766 AC XY: 55712 AN XY: 726952

African (AFR) AF: 0.0400 AC: 1340 AN: 33460

American (AMR) AF: 0.0508 AC: 2272 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 3248 AN: 26118

East Asian (EAS) AF: 0.0956 AC: 3796 AN: 39694

South Asian (SAS) AF: 0.176 AC: 15203 AN: 86170

European-Finnish (FIN) AF: 0.0570 AC: 3045 AN: 53404

Middle Eastern (MID) AF: 0.101 AC: 563 AN: 5590

European-Non Finnish (NFE) AF: 0.0649 AC: 72131 AN: 1111844

Other (OTH) AF: 0.0848 AC: 5118 AN: 60348

GnomAD4 genome AF: 0.0653 AC: 9945 AN: 152304 Hom.: 381 Cov.: 32 AF XY: 0.0671 AC XY: 5000 AN XY: 74466

African (AFR) AF: 0.0413 AC: 1716 AN: 41572

American (AMR) AF: 0.0654 AC: 1000 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3472

East Asian (EAS) AF: 0.132 AC: 686 AN: 5178

South Asian (SAS) AF: 0.168 AC: 810 AN: 4822

European-Finnish (FIN) AF: 0.0552 AC: 586 AN: 10614

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0653 AC: 4443 AN: 68024

Other (OTH) AF: 0.0884 AC: 187 AN: 2116

Alfa AF: 0.0696 Hom.: 127

Bravo AF: 0.0612

TwinsUK AF: 0.0688 AC: 255

ALSPAC AF: 0.0698 AC: 269

ESP6500AA AF: 0.0336 AC: 148

ESP6500EA AF: 0.0723 AC: 622

ExAC AF: 0.0863 AC: 10479

Asia WGS AF: 0.198 AC: 688 AN: 3478

EpiCase AF: 0.0742

EpiControl AF: 0.0724

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Benign	0.96
Eigen	Benign	-0.026
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.19	N
MetaRNN	Benign	0.0017	T;T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		1.5
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-4.5	D;D;.;.
REVEL	Benign	0.17
Sift	Uncertain	0.013	D;D;.;.
Sift4G	Uncertain	0.0020	D;D;D;D
Vest4		0.20
MPC		1.9
ClinPred		0.047	T
GERP RS		2.2
gMVP		0.72
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3894326; hg19: chr19-5843784; COSMIC: COSV54605243; COSMIC: COSV54605243;