chr19-48751019-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001384359.1(FUT1):c.263G>A(p.Arg88Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000101 in 1,589,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000097 ( 0 hom. )
Consequence
FUT1
NM_001384359.1 missense
NM_001384359.1 missense
Scores
7
3
4
Clinical Significance
Conservation
PhyloP100: 4.79
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.981
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FUT1 | NM_001384359.1 | c.263G>A | p.Arg88Gln | missense_variant | 2/2 | ENST00000645652.2 | |
FUT1 | NM_000148.4 | c.263G>A | p.Arg88Gln | missense_variant | 4/4 | ||
FUT1 | NM_001329877.1 | c.263G>A | p.Arg88Gln | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FUT1 | ENST00000645652.2 | c.263G>A | p.Arg88Gln | missense_variant | 2/2 | NM_001384359.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152206Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000129 AC: 3AN: 233042Hom.: 0 AF XY: 0.00000799 AC XY: 1AN XY: 125128
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GnomAD4 exome AF: 0.00000974 AC: 14AN: 1437784Hom.: 0 Cov.: 33 AF XY: 0.0000112 AC XY: 8AN XY: 711830
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74364
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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 | Feb 14, 2023 | The c.263G>A (p.R88Q) alteration is located in exon 4 (coding exon 1) of the FUT1 gene. This alteration results from a G to A substitution at nucleotide position 263, causing the arginine (R) at amino acid position 88 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D
PrimateAI
Benign
T
Polyphen
D;D
Vest4
0.74
MutPred
Loss of methylation at R88 (P = 0.0175);Loss of methylation at R88 (P = 0.0175);
MVP
0.99
MPC
1.4
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at