rs202018501

Variant names:

• chr19-5843929-C-A
• rs202018501
• ENST00000303225.12:c.911G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-5843929-C-A
• chr19-5843929-C-G
• chr19-5843929-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000149.4(FUT3):​c.911G>T​(p.Arg304Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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 0.0000066 (0 hom., cov: 32)
• Consequence: FUT3 NM_000149.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.112293065).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT3	NM_000149.4	c.911G>T	p.Arg304Leu	missense_variant	Exon 3 of 3		NP_000140.1
FUT3	NM_001097639.3	c.911G>T	p.Arg304Leu	missense_variant	Exon 3 of 3		NP_001091108.3
FUT3	NM_001097640.3	c.911G>T	p.Arg304Leu	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.911G>T	p.Arg304Leu	missense_variant	Exon 3 of 3	1		ENSP00000305603.5
FUT3	ENST00000458379.7	c.911G>T	p.Arg304Leu	missense_variant	Exon 2 of 2	1		ENSP00000416443.1
FUT3	ENST00000589620.6	c.911G>T	p.Arg304Leu	missense_variant	Exon 3 of 3	1		ENSP00000465804.1
FUT3	ENST00000589918.5	c.911G>T	p.Arg304Leu	missense_variant	Exon 3 of 3	1		ENSP00000468123.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152098 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

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.: 34

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152098 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74296

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

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	0.085
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.95
DANN	Benign	0.85
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.033	N
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.9	N;N;.;.
REVEL	Benign	0.013
Sift	Benign	0.17	T;T;.;.
Sift4G	Benign	0.33	T;T;T;T
Vest4		0.17
MutPred		0.46		Loss of methylation at K300 (P = 0.0479);Loss of methylation at K300 (P = 0.0479);Loss of methylation at K300 (P = 0.0479);Loss of methylation at K300 (P = 0.0479);
MVP		0.16
MPC		0.72
ClinPred		0.085	T
GERP RS		-0.36
gMVP		0.34

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: rs202018501; hg19: chr19-5843940;