rs565590532

Variant names:

• chr19-5844108-G-A
• rs565590532
• NM_001097639.3:c.732C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001097639.3(FUT3):​c.732C>T​(p.Tyr244Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,611,856 control chromosomes in the GnomAD database, including 15 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0068 (8 hom., cov: 31)
  • Exomes 𝑓: 0.00064 (7 hom.)
• Consequence: FUT3 NM_001097639.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.45
• Publications: 0 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 19-5844108-G-A is Benign according to our data. Variant chr19-5844108-G-A is described in ClinVar as Benign. ClinVar VariationId is 718641.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.45 with no splicing effect.

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.732C>T	p.Tyr244Tyr	synonymous	Exon 3 of 3	NP_001091108.3	A8K737
	FUT3	NM_000149.4		c.732C>T	p.Tyr244Tyr	synonymous	Exon 3 of 3	NP_000140.1	A8K737
	FUT3	NM_001097640.3		c.732C>T	p.Tyr244Tyr	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.732C>T	p.Tyr244Tyr	synonymous	Exon 3 of 3	ENSP00000305603.5	P21217
	FUT3	ENST00000458379.7	TSL:1	c.732C>T	p.Tyr244Tyr	synonymous	Exon 2 of 2	ENSP00000416443.1	P21217
	FUT3	ENST00000589620.6	TSL:1	c.732C>T	p.Tyr244Tyr	synonymous	Exon 3 of 3	ENSP00000465804.1	P21217

Frequencies

GnomAD3 genomes AF: 0.00679 AC: 1030 AN: 151738 Hom.: 8 Cov.: 31

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00271

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00121

Gnomad OTH AF: 0.00720

GnomAD2 exomes AF: 0.000899 AC: 226 AN: 251334 AF XY: 0.000810

Gnomad AFR exome AF: 0.00746

Gnomad AMR exome AF: 0.000810

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00103

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000325

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000639 AC: 933 AN: 1460004 Hom.: 7 Cov.: 34 AF XY: 0.000633 AC XY: 460 AN XY: 726366

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

African (AFR) AF: 0.00877 AC: 290 AN: 33070

American (AMR) AF: 0.00123 AC: 55 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00181 AC: 72 AN: 39694

South Asian (SAS) AF: 0.00132 AC: 114 AN: 86196

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53418

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5758

European-Non Finnish (NFE) AF: 0.000292 AC: 324 AN: 1110742

Other (OTH) AF: 0.00123 AC: 74 AN: 60308

⚠️ 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: 0.00682 AC: 1036 AN: 151852 Hom.: 8 Cov.: 31 AF XY: 0.00640 AC XY: 475 AN XY: 74232

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

African (AFR) AF: 0.0204 AC: 841 AN: 41230

American (AMR) AF: 0.00445 AC: 68 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00271 AC: 14 AN: 5160

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00121 AC: 82 AN: 67962

Other (OTH) AF: 0.00712 AC: 15 AN: 2106

⚠️ 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.

Alfa AF: 0.00363 Hom.: 2

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.6
DANN	Benign	0.63
PhyloP100		2.4
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: rs565590532; hg19: chr19-5844119;