1-59457044-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018291.5(FGGY):ā€‹c.638A>Gā€‹(p.Glu213Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,688 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000068 ( 0 hom. )

Consequence

FGGY
NM_018291.5 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.62
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FGGYNM_018291.5 linkuse as main transcriptc.638A>G p.Glu213Gly missense_variant 6/16 ENST00000303721.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FGGYENST00000303721.12 linkuse as main transcriptc.638A>G p.Glu213Gly missense_variant 6/161 NM_018291.5 P1Q96C11-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461688
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
727154
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.00
Gnomad4 NFE exome
AF:
0.00000809
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000579
Hom.:
0
Bravo
AF:
0.00000756
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0

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 submitterclinical testingAmbry GeneticsJan 23, 2024The c.638A>G (p.E213G) alteration is located in exon 6 (coding exon 5) of the FGGY gene. This alteration results from a A to G substitution at nucleotide position 638, causing the glutamic acid (E) at amino acid position 213 to be replaced by a glycine (G). 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
0.086
BayesDel_addAF
Uncertain
0.16
D
BayesDel_noAF
Uncertain
-0.010
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.067
.;T;.
Eigen
Benign
-0.0026
Eigen_PC
Benign
0.20
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Benign
0.025
T
MetaRNN
Uncertain
0.54
D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.86
L;L;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Benign
0.41
T
PROVEAN
Uncertain
-2.6
D;D;N
REVEL
Benign
0.25
Sift
Benign
0.42
T;T;T
Sift4G
Benign
0.50
T;T;T
Polyphen
0.054
B;B;.
Vest4
0.71
MutPred
0.60
Loss of stability (P = 0.0271);Loss of stability (P = 0.0271);.;
MVP
0.35
MPC
0.038
ClinPred
0.98
D
GERP RS
5.2
Varity_R
0.33
gMVP
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.24
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.24
Position offset: 32

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.

Other links and lift over

dbSNP: rs748586572; hg19: chr1-59922716; API