chr19-5844332-C-T

Position:

• chr19-5844332-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000149.4(FUT3):​c.508G>A​(p.Gly170Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0465 in 1,613,770 control chromosomes in the GnomAD database, including 5,663 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.11 (1744 hom., cov: 31)
  • Exomes 𝑓: 0.040 (3919 hom.)
• Consequence: FUT3 NM_000149.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.10

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018966794).
• BP6: Variant 19-5844332-C-T is Benign according to our data. Variant chr19-5844332-C-T is described in ClinVar as [Benign]. Clinvar id is 242700.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FUT3	NM_000149.4	c.508G>A	p.Gly170Ser	missense_variant	3/3		NP_000140.1
FUT3	NM_001097639.3	c.508G>A	p.Gly170Ser	missense_variant	3/3		NP_001091108.3
FUT3	NM_001097640.3	c.508G>A	p.Gly170Ser	missense_variant	3/3		NP_001091109.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FUT3	ENST00000303225.12	c.508G>A	p.Gly170Ser	missense_variant	3/3	1		ENSP00000305603.5
FUT3	ENST00000458379.7	c.508G>A	p.Gly170Ser	missense_variant	2/2	1		ENSP00000416443.1
FUT3	ENST00000589620.6	c.508G>A	p.Gly170Ser	missense_variant	3/3	1		ENSP00000465804.1
FUT3	ENST00000589918.5	c.508G>A	p.Gly170Ser	missense_variant	3/3	1		ENSP00000468123.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16707 AN: 151836 Hom.: 1728 Cov.: 31

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.0618

Gnomad FIN AF: 0.0664

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0193

Gnomad OTH AF: 0.0977

GnomAD3 exomes AF: 0.0851 AC: 21246 AN: 249570 Hom.: 1989 AF XY: 0.0728 AC XY: 9845 AN XY: 135240

Gnomad AFR exome AF: 0.256

Gnomad AMR exome AF: 0.242

Gnomad ASJ exome AF: 0.0201

Gnomad EAS exome AF: 0.167

Gnomad SAS exome AF: 0.0544

Gnomad FIN exome AF: 0.0637

Gnomad NFE exome AF: 0.0199

Gnomad OTH exome AF: 0.0570

GnomAD4 exome AF: 0.0398 AC: 58216 AN: 1461816 Hom.: 3919 Cov.: 36 AF XY: 0.0382 AC XY: 27746 AN XY: 727212

Gnomad4 AFR exome AF: 0.255

Gnomad4 AMR exome AF: 0.235

Gnomad4 ASJ exome AF: 0.0182

Gnomad4 EAS exome AF: 0.203

Gnomad4 SAS exome AF: 0.0527

Gnomad4 FIN exome AF: 0.0613

Gnomad4 NFE exome AF: 0.0178

Gnomad4 OTH exome AF: 0.0479

GnomAD4 genome AF: 0.110 AC: 16744 AN: 151954 Hom.: 1744 Cov.: 31 AF XY: 0.114 AC XY: 8438 AN XY: 74250

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.0614

Gnomad4 FIN AF: 0.0664

Gnomad4 NFE AF: 0.0193

Gnomad4 OTH AF: 0.0986

Alfa AF: 0.0521 Hom.: 320

Bravo AF: 0.127

ESP6500AA AF: 0.247 AC: 1082

ESP6500EA AF: 0.0172 AC: 147

ExAC AF: 0.0815 AC: 9889

EpiCase AF: 0.0148

EpiControl AF: 0.0152

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

FUT3-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Uncertain	1.0
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.81	D
MetaRNN	Benign	0.0019	T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-5.7	D;D;.;.
REVEL	Benign	0.26
Sift	Uncertain	0.011	D;D;.;.
Sift4G	Pathogenic	0.0	D;D;D;D
Vest4		0.12
MPC		1.4
ClinPred		0.027	T
GERP RS		2.2
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3745635; hg19: chr19-5844343; COSMIC: COSV54604546; COSMIC: COSV54604546;