1-59346346-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_018291.5(FGGY):​c.413G>T​(p.Gly138Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,459,688 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: not found (cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

FGGY
NM_018291.5 missense

Scores

12
4
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.71
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 Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.991

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FGGYNM_018291.5 linkuse as main transcriptc.413G>T p.Gly138Val missense_variant 4/16 ENST00000303721.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FGGYENST00000303721.12 linkuse as main transcriptc.413G>T p.Gly138Val missense_variant 4/161 NM_018291.5 P1Q96C11-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
250796
Hom.:
0
AF XY:
0.0000369
AC XY:
5
AN XY:
135536
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000981
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1459688
Hom.:
0
Cov.:
30
AF XY:
0.0000151
AC XY:
11
AN XY:
726150
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000139
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000330
AC:
4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Pathogenic
0.33
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.23
T;.;T
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Benign
0.70
D
LIST_S2
Pathogenic
1.0
D;D;D
M_CAP
Uncertain
0.24
D
MetaRNN
Pathogenic
0.99
D;D;D
MetaSVM
Uncertain
0.58
D
MutationAssessor
Pathogenic
4.1
.;H;H
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.62
T
PROVEAN
Pathogenic
-8.8
D;D;D
REVEL
Pathogenic
0.77
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
.;D;D
Vest4
0.95, 0.96
MutPred
0.94
Gain of catalytic residue at G138 (P = 0.0894);Gain of catalytic residue at G138 (P = 0.0894);Gain of catalytic residue at G138 (P = 0.0894);
MVP
0.60
MPC
0.22
ClinPred
1.0
D
GERP RS
5.5
Varity_R
0.98
gMVP
0.92

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs779045174; hg19: chr1-59812018; API