chr5-180316810-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_005110.4(GFPT2):c.1106G>A(p.Arg369Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000356 in 1,614,046 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 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00038 ( 0 hom. )
Consequence
GFPT2
NM_005110.4 missense
NM_005110.4 missense
Scores
9
9
1
Clinical Significance
Conservation
PhyloP100: 7.80
Genes affected
GFPT2 (HGNC:4242): (glutamine-fructose-6-phosphate transaminase 2) Predicted to enable glutamine-fructose-6-phosphate transaminase (isomerizing) activity. Predicted to be involved in UDP-N-acetylglucosamine metabolic process; fructose 6-phosphate metabolic process; and protein N-linked glycosylation. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Predicted to be located in cytosol. Implicated in type 2 diabetes mellitus. [provided by Alliance of Genome Resources, Apr 2022]
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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, 0.822
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GFPT2 | NM_005110.4 | c.1106G>A | p.Arg369Gln | missense_variant | 12/19 | ENST00000253778.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GFPT2 | ENST00000253778.13 | c.1106G>A | p.Arg369Gln | missense_variant | 12/19 | 1 | NM_005110.4 | P1 | |
GFPT2 | ENST00000520165.1 | n.611G>A | non_coding_transcript_exon_variant | 4/4 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152180Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000156 AC: 39AN: 249410Hom.: 0 AF XY: 0.000163 AC XY: 22AN XY: 135302
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GnomAD4 exome AF: 0.000379 AC: 554AN: 1461748Hom.: 0 Cov.: 31 AF XY: 0.000375 AC XY: 273AN XY: 727176
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GnomAD4 genome AF: 0.000138 AC: 21AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74474
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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 | Jan 26, 2022 | The c.1106G>A (p.R369Q) alteration is located in exon 12 (coding exon 12) of the GFPT2 gene. This alteration results from a G to A substitution at nucleotide position 1106, causing the arginine (R) at amino acid position 369 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
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
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