19-5844638-G-A

Variant names:

• chr19-5844638-G-A
• rs812936
• NM_001097639.3:c.202C>T

Variant summary

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

The NM_001097639.3(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. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R68G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.84 (51983 hom., cov: 21)
  • Exomes 𝑓: 0.83 (494194 hom.)
• Consequence: FUT3 NM_001097639.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.04
• Publications: 79 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=2.923837E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001097639.3. 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
	FUT3	NM_001097639.3	MANE Select	c.202C>T	p.Arg68Trp	missense	Exon 3 of 3	NP_001091108.3	A8K737
	FUT3	NM_000149.4		c.202C>T	p.Arg68Trp	missense	Exon 3 of 3	NP_000140.1	A8K737
	FUT3	NM_001097640.3		c.202C>T	p.Arg68Trp	missense	Exon 3 of 3	NP_001091109.3	A8K737

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT3	ENST00000303225.12	TSL:1	c.202C>T	p.Arg68Trp	missense	Exon 3 of 3	ENSP00000305603.5	P21217
	FUT3	ENST00000458379.7	TSL:1	c.202C>T	p.Arg68Trp	missense	Exon 2 of 2	ENSP00000416443.1	P21217
	FUT3	ENST00000589620.6	TSL:1	c.202C>T	p.Arg68Trp	missense	Exon 3 of 3	ENSP00000465804.1	P21217

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

GnomAD2 exomes AF: 0.830 AC: 208584 AN: 251236 AF XY: 0.824

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 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

African (AFR) AF: 0.890 AC: 29661 AN: 33320

American (AMR) AF: 0.893 AC: 39812 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 19555 AN: 25396

East Asian (EAS) AF: 0.982 AC: 38987 AN: 39692

South Asian (SAS) AF: 0.819 AC: 70480 AN: 86038

European-Finnish (FIN) AF: 0.807 AC: 42404 AN: 52546

Middle Eastern (MID) AF: 0.786 AC: 4429 AN: 5632

European-Non Finnish (NFE) AF: 0.823 AC: 904789 AN: 1099156

Other (OTH) AF: 0.835 AC: 49765 AN: 59600

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

African (AFR) AF: 0.884 AC: 35481 AN: 40126

American (AMR) AF: 0.851 AC: 12588 AN: 14784

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2584 AN: 3438

East Asian (EAS) AF: 0.970 AC: 4719 AN: 4864

South Asian (SAS) AF: 0.831 AC: 3773 AN: 4540

European-Finnish (FIN) AF: 0.801 AC: 8079 AN: 10092

Middle Eastern (MID) AF: 0.771 AC: 222 AN: 288

European-Non Finnish (NFE) AF: 0.806 AC: 53999 AN: 66976

Other (OTH) AF: 0.795 AC: 1634 AN: 2056

Alfa AF: 0.814 Hom.: 137507

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 v4.9

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
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0000029	T
MetaSVM	Benign	-0.96	T
PhyloP100		4.0
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	14	N
REVEL	Benign	0.070
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.064
MPC		0.57
ClinPred		0.0037	T
GERP RS		2.3
gMVP		0.91
Mutation Taster		=98/2	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: rs812936; hg19: chr19-5844649; COSMIC: COSV54606175; COSMIC: COSV54606175;