chr1-59457019-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018291.5(FGGY):​c.613A>T​(p.Ser205Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000415 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S205N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

FGGY
NM_018291.5 missense

Scores

2
13
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.89

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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FGGYNM_018291.5 linkc.613A>T p.Ser205Cys 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.613A>T p.Ser205Cys missense_variant Exon 6 of 16 1 NM_018291.5 ENSP00000305922.8 Q96C11-1

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152222
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000159
AC:
4
AN:
251410
AF XY:
0.0000294
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000424
AC:
62
AN:
1461810
Hom.:
0
Cov.:
30
AF XY:
0.0000468
AC XY:
34
AN XY:
727208
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33478
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39690
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53402
Middle Eastern (MID)
AF:
0.000173
AC:
1
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000540
AC:
60
AN:
1111968
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60388
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.444
Heterozygous variant carriers
0
3
7
10
14
17
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
AF:
0.0000328
AC:
5
AN:
152222
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74378
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41458
American (AMR)
AF:
0.00
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5190
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10626
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000735
AC:
5
AN:
68040
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome 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
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000567
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.000164
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 06, 2021
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.613A>T (p.S205C) alteration is located in exon 6 (coding exon 5) of the FGGY gene. This alteration results from a A to T substitution at nucleotide position 613, causing the serine (S) at amino acid position 205 to be replaced by a cysteine (C). 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
0.12
BayesDel_addAF
Uncertain
0.050
T
BayesDel_noAF
Uncertain
-0.060
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
.;T;.
Eigen
Pathogenic
0.71
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Benign
0.054
D
MetaRNN
Uncertain
0.69
D;D;D
MetaSVM
Uncertain
-0.12
T
MutationAssessor
Pathogenic
2.9
M;M;.
PhyloP100
5.9
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-3.7
D;D;D
REVEL
Uncertain
0.34
Sift
Uncertain
0.010
D;D;D
Sift4G
Uncertain
0.016
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.76
MVP
0.45
MPC
0.19
ClinPred
0.94
D
GERP RS
5.2
Varity_R
0.71
gMVP
0.64
Mutation Taster
=62/38
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: rs371851463; hg19: chr1-59922691; API