19-48703387-A-T

Variant names:

• chr19-48703387-A-T
• NM_000511.6:c.431A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000511.6(FUT2):​c.431A>T​(p.Tyr144Phe) variant causes a missense 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FUT2 NM_000511.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.08

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25727123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT2	NM_000511.6	c.431A>T	p.Tyr144Phe	missense_variant	Exon 2 of 2	ENST00000425340.3	NP_000502.4
FUT2	NM_001097638.3	c.431A>T	p.Tyr144Phe	missense_variant	Exon 2 of 2		NP_001091107.1
LOC105447645	NR_131188.1	n.462T>A		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUT2	ENST00000425340.3	c.431A>T	p.Tyr144Phe	missense_variant	Exon 2 of 2	1	NM_000511.6	ENSP00000387498.2
FUT2	ENST00000522966.2	c.431A>T	p.Tyr144Phe	missense_variant	Exon 2 of 2	2		ENSP00000430227.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 76

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 10, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.431A>T (p.Y144F) alteration is located in exon 2 (coding exon 1) of the FUT2 gene. This alteration results from a A to T substitution at nucleotide position 431, causing the tyrosine (Y) at amino acid position 144 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	11
DANN	Benign	0.16
DEOGEN2	Benign	0.025	.;T;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.80	.;.;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.0	.;M;M
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Uncertain	0.42
Sift	Benign	0.80	T;T;T
Sift4G	Benign	0.65	T;T;T
Polyphen		0.019	.;B;B
Vest4		0.21, 0.25
MutPred		0.69		Loss of phosphorylation at T148 (P = 0.2264);Loss of phosphorylation at T148 (P = 0.2264);Loss of phosphorylation at T148 (P = 0.2264);
MVP		0.89
MPC		0.26
ClinPred		0.026	T
GERP RS		-0.40
Varity_R		0.092
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-49206644;