19-5844638-G-C

Variant summary

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

The NM_001382749.2(FUT3):c.202C>G(p.Arg68Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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 0.0 (0 hom., cov: 21)
  • Failed GnomAD Quality Control
• 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 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/exons	MANE	UniProt
FUT3	NM_001097639.3	c.202C>G	p.Trp68Gly	missense_variant	3/3	ENST00000709635.1
FUT3	NM_001382749.2	c.202C>G	p.Arg68Gly	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FUT3	ENST00000303225.12	c.202C>G	p.Arg68Gly	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 148072 Hom.: 0 Cov.: 21 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 52

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 148072 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 71962

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
Cadd	Benign	19
Dann	Benign	0.92
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.68	D
M_CAP	Benign	0.0048	T
MetaRNN	Uncertain	0.47	T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.86	N;N;.;.;.;.
REVEL	Benign	0.26
Sift	Uncertain	0.0050	D;D;.;.;.;.
Sift4G	Uncertain	0.0040	D;D;D;D;D;D
Vest4		0.23
MutPred		0.65		Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);
MVP		0.17
MPC		0.71
ClinPred		0.43	T
GERP RS		2.3
gMVP		0.95

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;