chr14-65615996-T-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_001371533.1(FUT8):c.222T>G(p.Ile74Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,613,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001371533.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FUT8 | NM_001371533.1 | c.222T>G | p.Ile74Met | missense_variant | 4/11 | ENST00000673929.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FUT8 | ENST00000673929.1 | c.222T>G | p.Ile74Met | missense_variant | 4/11 | NM_001371533.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152226Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000919 AC: 23AN: 250374Hom.: 0 AF XY: 0.0000961 AC XY: 13AN XY: 135312
GnomAD4 exome AF: 0.000126 AC: 184AN: 1460666Hom.: 0 Cov.: 30 AF XY: 0.000124 AC XY: 90AN XY: 726688
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152344Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74506
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 07, 2022 | This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 74 of the FUT8 protein (p.Ile74Met). This variant is present in population databases (rs368415291, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with FUT8-related conditions. ClinVar contains an entry for this variant (Variation ID: 916157). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 05, 2022 | The c.222T>G (p.I74M) alteration is located in exon 4 (coding exon 2) of the FUT8 gene. This alteration results from a T to G substitution at nucleotide position 222, causing the isoleucine (I) at amino acid position 74 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Congenital disorder of glycosylation with defective fucosylation 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 09, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at