chr1-59554187-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_018291.5(FGGY):c.863G>A(p.Arg288Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,613,476 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000032 ( 0 hom. )
Consequence
FGGY
NM_018291.5 missense
NM_018291.5 missense
Scores
6
4
9
Clinical Significance
Conservation
PhyloP100: 7.52
Genes affected
FGGY (HGNC:25610): (FGGY carbohydrate kinase domain containing) This gene encodes a protein that phosphorylates carbohydrates such as ribulose, ribitol, and L-arabinitol. Genome-wide association studies in some populations have found an association between polymorphisms in this gene and sporadic amyotrophic lateral sclerosis, but studies of other populations have not been able to replicate this association. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]
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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, 0.767
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FGGY | NM_018291.5 | c.863G>A | p.Arg288Gln | missense_variant | 8/16 | ENST00000303721.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FGGY | ENST00000303721.12 | c.863G>A | p.Arg288Gln | missense_variant | 8/16 | 1 | NM_018291.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152142Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250942Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135666
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GnomAD4 exome AF: 0.0000322 AC: 47AN: 1461334Hom.: 0 Cov.: 30 AF XY: 0.0000303 AC XY: 22AN XY: 726910
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74318
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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 | Jun 10, 2022 | The c.863G>A (p.R288Q) alteration is located in exon 8 (coding exon 7) of the FGGY gene. This alteration results from a G to A substitution at nucleotide position 863, causing the arginine (R) at amino acid position 288 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
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;.
Vest4
MutPred
Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);.;
MVP
MPC
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