ENST00000303225.12:c.612A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The ENST00000303225.12(FUT3):c.612A>G(p.Ser204Ser) 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. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. 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
ENST00000303225.12 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -7.57

Publications

7 publications found

Variant links:

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]

FUT3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000303225.12. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FUT3	NM_001097639.3	MANE Select	c.612A>G	p.Ser204Ser	synonymous	Exon 3 of 3	NP_001091108.3	A8K737
FUT3	NM_000149.4		c.612A>G	p.Ser204Ser	synonymous	Exon 3 of 3	NP_000140.1	A8K737
FUT3	NM_001097640.3		c.612A>G	p.Ser204Ser	synonymous	Exon 3 of 3	NP_001091109.3	A8K737

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FUT3	ENST00000303225.12	TSL:1	c.612A>G	p.Ser204Ser	synonymous	Exon 3 of 3	ENSP00000305603.5	P21217
FUT3	ENST00000458379.7	TSL:1	c.612A>G	p.Ser204Ser	synonymous	Exon 2 of 2	ENSP00000416443.1	P21217
FUT3	ENST00000589620.6	TSL:1	c.612A>G	p.Ser204Ser	synonymous	Exon 3 of 3	ENSP00000465804.1	P21217

Frequencies

GnomAD3 genomes

AF:

0.0193

AC:

2930

AN:

151692

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00448

AC:

1113

AN:

248410

AF XY:

0.00384

show subpopulations

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 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.:

AF XY:

0.00525

AC XY:

3769

AN XY:

718152

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0190

AC:

616

AN:

32470

American (AMR)

AF:

0.00700

AC:

311

AN:

44460

Ashkenazi Jewish (ASJ)

AF:

0.00940

AC:

243

AN:

25862

East Asian (EAS)

AF:

0.0212

AC:

836

AN:

39422

South Asian (SAS)

AF:

0.00376

AC:

323

AN:

85886

European-Finnish (FIN)

AF:

0.00549

AC:

292

AN:

53208

Middle Eastern (MID)

AF:

0.00630

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.00414

AC:

4543

AN:

1096210

Other (OTH)

AF:

0.00769

AC:

459

AN:

59670

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.345

Heterozygous variant carriers

502

1005

1507

2010

2512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0194

AC:

2945

AN:

151812

Hom.:

Cov.:

AF XY:

0.0187

AC XY:

1384

AN XY:

74198

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0365

AC:

1506

AN:

41286

American (AMR)

AF:

0.0184

AC:

281

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0110

AC:

AN:

3470

East Asian (EAS)

AF:

0.0244

AC:

125

AN:

5128

South Asian (SAS)

AF:

0.00602

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00708

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0120

AC:

813

AN:

67930

Other (OTH)

AF:

0.0227

AC:

AN:

2110

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.381

Heterozygous variant carriers

127

254

380

507

634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00575

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

FUT3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.18

(source)

DANN

Benign

0.28

PhyloP100

-7.6

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over