chr19-48703949-A-C

Variant names:

• chr19-48703949-A-C
• NM_000511.6:c.993A>C
• FUT2 p.Thr331Thr

Variant summary

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

The NM_000511.6(FUT2):​c.993A>C​(p.Thr331Thr) 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. T331T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FUT2 NM_000511.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 0 publications found

Genes affected

FUT2 (HGNC:4013): (fucosyltransferase 2 (H blood group)) This gene is one of two encoding the galactoside 2-L-fucosyltransferase enzyme. The encoded protein is important for the final step in the soluble ABO blood group antigen synthesis pathway. It is also involved in cell-cell interaction, cell surface expression, and cell proliferation. Mutations in this gene are a cause of the H-Bombay blood group where red blood cells lack the H antigen. [provided by RefSeq, May 2022]

LOC105447645 (HGNC:):

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=-0.99).
• BP7: Synonymous conserved (PhyloP=-1.91 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000511.6. 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
	FUT2	NM_000511.6	MANE Select	c.993A>C	p.Thr331Thr	synonymous	Exon 2 of 2	NP_000502.4	A8K2L2
	FUT2	NM_001097638.3		c.993A>C	p.Thr331Thr	synonymous	Exon 2 of 2	NP_001091107.1	Q10981
	LOC105447645	NR_131188.1		n.-101T>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT2	ENST00000425340.3	TSL:1 MANE Select	c.993A>C	p.Thr331Thr	synonymous	Exon 2 of 2	ENSP00000387498.2	Q10981
	FUT2	ENST00000522966.2	TSL:2	c.993A>C	p.Thr331Thr	synonymous	Exon 2 of 2	ENSP00000430227.2	Q10981
	FUT2	ENST00000960751.1		c.993A>C	p.Thr331Thr	synonymous	Exon 3 of 3	ENSP00000630810.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.21
DANN	Benign	0.40
PhyloP100		-1.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-49207206;