1-59457015-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018291.5(FGGY):​c.609C>A​(p.Asp203Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

FGGY
NM_018291.5 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.148
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37149656).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FGGYNM_018291.5 linkc.609C>A p.Asp203Glu missense_variant Exon 6 of 16 ENST00000303721.12 NP_060761.3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FGGYENST00000303721.12 linkc.609C>A p.Asp203Glu missense_variant Exon 6 of 16 1 NM_018291.5 ENSP00000305922.8 Q96C11-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 21, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.609C>A (p.D203E) alteration is located in exon 6 (coding exon 5) of the FGGY gene. This alteration results from a C to A substitution at nucleotide position 609, causing the aspartic acid (D) at amino acid position 203 to be replaced by a glutamic acid (E). 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
0.31
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.080
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.061
.;T;.
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.29
FATHMM_MKL
Benign
0.71
D
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Benign
0.033
D
MetaRNN
Benign
0.37
T;T;T
MetaSVM
Benign
-0.52
T
MutationAssessor
Pathogenic
3.0
M;M;.
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-2.2
N;N;N
REVEL
Uncertain
0.36
Sift
Benign
0.043
D;D;D
Sift4G
Uncertain
0.036
D;D;T
Polyphen
0.99
D;D;.
Vest4
0.51
MutPred
0.71
Gain of methylation at K200 (P = 0.0775);Gain of methylation at K200 (P = 0.0775);.;
MVP
0.13
MPC
0.037
ClinPred
0.99
D
GERP RS
-1.1
Varity_R
0.53
gMVP
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-59922687; API