19-5844228-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001382749.2(FUT3):c.612A>G(p.Ser204=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 151,812 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (41 hom., cov: 31)
  • Exomes 𝑓: 0.0053 (150 hom.)
  • Failed GnomAD Quality Control
• Consequence: FUT3 NM_001382749.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -7.57

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 19-5844228-T-C is Benign according to our data. Variant chr19-5844228-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 773080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-7.57 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0194 (2945/151812) while in subpopulation AFR AF= 0.0365 (1506/41286). AF 95% confidence interval is 0.0349. There are 41 homozygotes in gnomad4. There are 1384 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 2930 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FUT3	NM_001097639.3	c.612A>G	p.Ser204=	synonymous_variant	3/3	ENST00000709635.1
FUT3	NM_001382749.2	c.612A>G	p.Ser204=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FUT3	ENST00000303225.12	c.612A>G	p.Ser204=	synonymous_variant	3/3	1		P1
FUT3	ENST00000458379.7	c.612A>G	p.Ser204=	synonymous_variant	2/2	1		P1
FUT3	ENST00000589620.6	c.612A>G	p.Ser204=	synonymous_variant	3/3	1		P1
FUT3	ENST00000589918.5	c.612A>G	p.Ser204=	synonymous_variant	3/3	1		P1

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2930 AN: 151692 Hom.: 41 Cov.: 31

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0184

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.0245

Gnomad SAS AF: 0.00623

Gnomad FIN AF: 0.00708

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.0230

GnomAD3 exomes AF: 0.00448 AC: 1113 AN: 248410 Hom.: 20 AF XY: 0.00384 AC XY: 515 AN XY: 134268

Gnomad AFR exome AF: 0.0142

Gnomad AMR exome AF: 0.00475

Gnomad ASJ exome AF: 0.00394

Gnomad EAS exome AF: 0.0130

Gnomad SAS exome AF: 0.00174

Gnomad FIN exome AF: 0.000700

Gnomad NFE exome AF: 0.00307

Gnomad OTH exome AF: 0.00610

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00531 AC: 7659 AN: 1442904 Hom.: 150 Cov.: 34 AF XY: 0.00525 AC XY: 3769 AN XY: 718152

Gnomad4 AFR exome AF: 0.0190

Gnomad4 AMR exome AF: 0.00700

Gnomad4 ASJ exome AF: 0.00940

Gnomad4 EAS exome AF: 0.0212

Gnomad4 SAS exome AF: 0.00376

Gnomad4 FIN exome AF: 0.00549

Gnomad4 NFE exome AF: 0.00414

Gnomad4 OTH exome AF: 0.00769

GnomAD4 genome AF: 0.0194 AC: 2945 AN: 151812 Hom.: 41 Cov.: 31 AF XY: 0.0187 AC XY: 1384 AN XY: 74198

Gnomad4 AFR AF: 0.0365

Gnomad4 AMR AF: 0.0184

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.0244

Gnomad4 SAS AF: 0.00602

Gnomad4 FIN AF: 0.00708

Gnomad4 NFE AF: 0.0120

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.00575 Hom.: 3

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

FUT3-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 01, 2023

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

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.18
Dann	Benign	0.28

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: rs28362465; hg19: chr19-5844239; COSMIC: COSV99744431; COSMIC: COSV99744431;