Variant 19-48750493-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001384359.1(FUT1):c.789C>A(p.Asn263Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

FUT1
NM_001384359.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.49

Variant links:

Genes affected

FUT1 (HGNC:4012): (fucosyltransferase 1 (H blood group)) This gene encodes a Golgi stack membrane protein that is involved in the creation of a precursor of the H antigen, which is required for the final step in the synthesis of soluble A and B antigens. This is one of two genes encoding the galactoside 2-L-fucosyltransferase enzyme. Mutations in this gene are a cause of the H-Bombay blood group. [provided by RefSeq, Aug 2016]

FUT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.813

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FUT1	NM_001384359.1 linkuse as main transcript	c.789C>A	p.Asn263Lys	missense_variant	2/2	ENST00000645652.2	NP_001371288.1
FUT1	NM_000148.4 linkuse as main transcript	c.789C>A	p.Asn263Lys	missense_variant	4/4		NP_000139.1	P19526Q6IZA2
FUT1	NM_001329877.1 linkuse as main transcript	c.789C>A	p.Asn263Lys	missense_variant	5/5		NP_001316806.1	P19526Q6IZA2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FUT1	ENST00000645652.2 linkuse as main transcript	c.789C>A	p.Asn263Lys	missense_variant	2/2		NM_001384359.1	ENSP00000494643.1		P19526

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000915

AC:

AN:

251302

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1461750

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000492

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2024

The c.789C>A (p.N263K) alteration is located in exon 4 (coding exon 1) of the FUT1 gene. This alteration results from a C to A substitution at nucleotide position 789, causing the asparagine (N) at amino acid position 263 to be replaced by a lysine (K). 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

Pathogenic

0.89

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

4.1

DANN

Uncertain

0.98

DEOGEN2

Benign

0.37

T;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.084

LIST_S2

Uncertain

0.94

.;D

M_CAP

Uncertain

0.27

MetaRNN

Pathogenic

0.81

D;D

MetaSVM

Pathogenic

0.97

MutationAssessor

Pathogenic

3.1

M;M

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-4.4

.;D

REVEL

Uncertain

0.60

Sift

Uncertain

0.0020

.;D

Sift4G

Uncertain

0.0060

.;D

Polyphen

1.0

D;D

Vest4

0.86

MutPred

0.74

Gain of methylation at N263 (P = 0.0194);Gain of methylation at N263 (P = 0.0194);

MVP

0.88

MPC

1.4

ClinPred

0.79

GERP RS

-5.3

Varity_R

0.93

gMVP

0.96

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over