Variant 19-48750654-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001384359.1(FUT1):c.628C>A(p.Arg210Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

FUT1
NM_001384359.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.58

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:

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ACMG classification

Classification made for transcript

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=0.1888493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FUT1	NM_001384359.1 linkuse as main transcript	c.628C>A	p.Arg210Ser	missense_variant	2/2	ENST00000645652.2	NP_001371288.1
FUT1	NM_000148.4 linkuse as main transcript	c.628C>A	p.Arg210Ser	missense_variant	4/4		NP_000139.1
FUT1	NM_001329877.1 linkuse as main transcript	c.628C>A	p.Arg210Ser	missense_variant	5/5		NP_001316806.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FUT1	ENST00000645652.2 linkuse as main transcript	c.628C>A	p.Arg210Ser	missense_variant	2/2		NM_001384359.1	ENSP00000494643	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460366

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726522

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000192

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 16, 2022

The c.628C>A (p.R210S) 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 628, causing the arginine (R) at amino acid position 210 to be replaced by a serine (S). 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

0.069

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.059

T;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.60

.;T

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.19

T;T

MetaSVM

Uncertain

0.43

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.4

.;N

REVEL

Uncertain

0.32

Sift

Benign

0.22

.;T

Sift4G

Benign

0.19

.;T

Polyphen

0.43

B;B

Vest4

0.17

MutPred

0.52

Loss of MoRF binding (P = 0.0215);Loss of MoRF binding (P = 0.0215);

MVP

0.92

MPC

0.68

ClinPred

0.45

GERP RS

2.3

Varity_R

0.068

gMVP

0.90

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