19-5844228-T-G

Variant names:

• chr19-5844228-T-G
• rs28362465
• NM_001097639.3:c.612A>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001097639.3(FUT3):​c.612A>C​(p.Ser204Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000335 in 1,610,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S204S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00033 (0 hom.)
• Consequence: FUT3 NM_001097639.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.57
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP7: Synonymous conserved (PhyloP=-7.57 with no splicing effect.
• BS2: High AC in GnomAd4 at 55 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001097639.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.000362 AC: 55 AN: 151882 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000213 AC: 53 AN: 248410 AF XY: 0.000216

Gnomad AFR exome AF: 0.000189

Gnomad AMR exome AF: 0.000466

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000385

Gnomad FIN exome AF: 0.0000467

Gnomad NFE exome AF: 0.000169

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.000332 AC: 484 AN: 1458340 Hom.: 0 Cov.: 34 AF XY: 0.000361 AC XY: 262 AN XY: 725500

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

African (AFR) AF: 0.0000901 AC: 3 AN: 33282

American (AMR) AF: 0.000381 AC: 17 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.000581 AC: 23 AN: 39602

South Asian (SAS) AF: 0.000499 AC: 43 AN: 86166

European-Finnish (FIN) AF: 0.000262 AC: 14 AN: 53336

Middle Eastern (MID) AF: 0.000522 AC: 3 AN: 5744

European-Non Finnish (NFE) AF: 0.000334 AC: 371 AN: 1109216

Other (OTH) AF: 0.000166 AC: 10 AN: 60244

⚠️ 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.

GnomAD4 genome AF: 0.000362 AC: 55 AN: 152000 Hom.: 0 Cov.: 31 AF XY: 0.000404 AC XY: 30 AN XY: 74294

African (AFR) AF: 0.000121 AC: 5 AN: 41394

American (AMR) AF: 0.00124 AC: 19 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4816

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000383 AC: 26 AN: 67970

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000111 Hom.: 3

Bravo AF: 0.000272

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.27
DANN	Benign	0.30
PhyloP100		-7.6
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs28362465; hg19: chr19-5844239;