19-5843811-T-C

Variant names:

• chr19-5843811-T-C
• rs199931170
• ENST00000303225.12:c.1029A>G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_000149.4(FUT3):​c.1029A>G​(p.Lys343Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000769 in 1,597,272 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00069 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00078 (4 hom.)
• Consequence: FUT3 NM_000149.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.744

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-5843811-T-C is Benign according to our data. Variant chr19-5843811-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 783813.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.744 with no splicing effect.
• BS2: High AC in GnomAd4 at 103 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT3	NM_000149.4	c.1029A>G	p.Lys343Lys	synonymous_variant	Exon 3 of 3		NP_000140.1
FUT3	NM_001097639.3	c.1029A>G	p.Lys343Lys	synonymous_variant	Exon 3 of 3		NP_001091108.3
FUT3	NM_001097640.3	c.1029A>G	p.Lys343Lys	synonymous_variant	Exon 3 of 3		NP_001091109.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUT3	ENST00000303225.12	c.1029A>G	p.Lys343Lys	synonymous_variant	Exon 3 of 3	1		ENSP00000305603.5
FUT3	ENST00000458379.7	c.1029A>G	p.Lys343Lys	synonymous_variant	Exon 2 of 2	1		ENSP00000416443.1
FUT3	ENST00000589620.6	c.1029A>G	p.Lys343Lys	synonymous_variant	Exon 3 of 3	1		ENSP00000465804.1
FUT3	ENST00000589918.5	c.1029A>G	p.Lys343Lys	synonymous_variant	Exon 3 of 3	1		ENSP00000468123.1

Frequencies

GnomAD3 genomes AF: 0.000687 AC: 102 AN: 148400 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000403

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00197

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000291

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000809

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000692 AC: 174 AN: 251324 Hom.: 0 AF XY: 0.000692 AC XY: 94 AN XY: 135862

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00147

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.000932

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000777 AC: 1126 AN: 1448750 Hom.: 4 Cov.: 33 AF XY: 0.000724 AC XY: 522 AN XY: 721040

Gnomad4 AFR exome AF: 0.00112

Gnomad4 AMR exome AF: 0.000225

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00652

Gnomad4 SAS exome AF: 0.000187

Gnomad4 FIN exome AF: 0.000327

Gnomad4 NFE exome AF: 0.000674

Gnomad4 OTH exome AF: 0.000751

GnomAD4 genome AF: 0.000693 AC: 103 AN: 148522 Hom.: 0 Cov.: 32 AF XY: 0.000580 AC XY: 42 AN XY: 72434

Gnomad4 AFR AF: 0.000747

Gnomad4 AMR AF: 0.000402

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00198

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000291

Gnomad4 NFE AF: 0.000809

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000835 Hom.: 0

EpiCase AF: 0.000600

EpiControl AF: 0.00107

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 06, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.78

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: rs199931170; hg19: chr19-5843822; COSMIC: COSV54604141; COSMIC: COSV54604141;