chr1-59346351-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018291.5(FGGY):​c.418G>A​(p.Val140Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,459,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V140L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

FGGY
NM_018291.5 missense

Scores

1
1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.86

Publications

2 publications found
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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20977119).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FGGYNM_018291.5 linkc.418G>A p.Val140Met missense_variant Exon 4 of 16 ENST00000303721.12 NP_060761.3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FGGYENST00000303721.12 linkc.418G>A p.Val140Met missense_variant Exon 4 of 16 1 NM_018291.5 ENSP00000305922.8 Q96C11-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000548
AC:
8
AN:
1459558
Hom.:
0
Cov.:
30
AF XY:
0.00000826
AC XY:
6
AN XY:
726088
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33376
American (AMR)
AF:
0.00
AC:
0
AN:
44686
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26114
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39688
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86162
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53406
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4318
European-Non Finnish (NFE)
AF:
0.00000720
AC:
8
AN:
1111620
Other (OTH)
AF:
0.00
AC:
0
AN:
60188
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.00000378
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.071
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
17
DANN
Benign
0.96
DEOGEN2
Benign
0.0057
T;.;T
Eigen
Benign
-0.50
Eigen_PC
Benign
-0.46
FATHMM_MKL
Benign
0.36
N
LIST_S2
Uncertain
0.92
D;D;D
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.21
T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Pathogenic
2.9
.;M;M
PhyloP100
3.9
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.35
N;N;N
REVEL
Benign
0.082
Sift
Benign
0.088
T;T;T
Sift4G
Benign
0.11
T;T;T
Polyphen
0.010, 0.0040
.;B;B
Vest4
0.27, 0.22
MutPred
0.44
Loss of catalytic residue at V140 (P = 0.0026);Loss of catalytic residue at V140 (P = 0.0026);Loss of catalytic residue at V140 (P = 0.0026);
MVP
0.15
MPC
0.031
ClinPred
0.61
D
GERP RS
2.6
Varity_R
0.11
gMVP
0.53
Mutation Taster
=83/17
polymorphism

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

Other links and lift over

dbSNP: rs761896156; hg19: chr1-59812023; API