chr19-5843865-C-G

Variant names:

• chr19-5843865-C-G
• rs61737303
• NM_001097639.3:c.975G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001097639.3(FUT3):​c.975G>C​(p.Thr325Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. T325T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FUT3 NM_001097639.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=-1.64 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.975G>C	p.Thr325Thr	synonymous	Exon 3 of 3	NP_001091108.3	A8K737
	FUT3	NM_000149.4		c.975G>C	p.Thr325Thr	synonymous	Exon 3 of 3	NP_000140.1	A8K737
	FUT3	NM_001097640.3		c.975G>C	p.Thr325Thr	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.975G>C	p.Thr325Thr	synonymous	Exon 3 of 3	ENSP00000305603.5	P21217
	FUT3	ENST00000458379.7	TSL:1	c.975G>C	p.Thr325Thr	synonymous	Exon 2 of 2	ENSP00000416443.1	P21217
	FUT3	ENST00000589620.6	TSL:1	c.975G>C	p.Thr325Thr	synonymous	Exon 3 of 3	ENSP00000465804.1	P21217

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.34
DANN	Benign	0.81
PhyloP100		-1.6

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: rs61737303; hg19: chr19-5843876;