NM_000511.6:c.390C>G

Variant names:

• chr19-48703346-C-G
• rs281377
• NM_000511.6:c.390C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000511.6(FUT2):​c.390C>G​(p.Asn130Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N130N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FUT2 NM_000511.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 83 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT2	NM_000511.6	MANE Select	c.390C>G	p.Asn130Lys	missense	Exon 2 of 2	NP_000502.4
	FUT2	NM_001097638.3		c.390C>G	p.Asn130Lys	missense	Exon 2 of 2	NP_001091107.1
	LOC105447645	NR_131188.1		n.503G>C		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT2	ENST00000425340.3	TSL:1 MANE Select	c.390C>G	p.Asn130Lys	missense	Exon 2 of 2	ENSP00000387498.2
	FUT2	ENST00000522966.2	TSL:2	c.390C>G	p.Asn130Lys	missense	Exon 2 of 2	ENSP00000430227.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 86

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Uncertain	0.79	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		-0.031
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.59
Sift	Uncertain	0.021	D
Sift4G	Benign	0.12	T
Polyphen		0.89	P
Vest4		0.29
MutPred		0.59		Gain of ubiquitination at N130 (P = 0.0219)
MVP		0.91
MPC		0.75
ClinPred		0.93	D
GERP RS		1.4
Varity_R		0.29
gMVP		0.30
Mutation Taster		=89/11	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: rs281377; hg19: chr19-49206603;