chr1-59457020-G-A

Variant summary

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

The NM_018291.5(FGGY):​c.614G>A​(p.Ser205Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000836 in 1,614,132 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 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. S205C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000072 ( 1 hom. )

Consequence

FGGY
NM_018291.5 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.35
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28914914).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FGGYNM_018291.5 linkuse as main transcriptc.614G>A p.Ser205Asn missense_variant 6/16 ENST00000303721.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FGGYENST00000303721.12 linkuse as main transcriptc.614G>A p.Ser205Asn missense_variant 6/161 NM_018291.5 P1Q96C11-1

Frequencies

GnomAD3 genomes
AF:
0.000191
AC:
29
AN:
152204
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00118
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000155
AC:
39
AN:
251408
Hom.:
0
AF XY:
0.000162
AC XY:
22
AN XY:
135874
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000694
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000123
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000718
AC:
105
AN:
1461810
Hom.:
1
Cov.:
30
AF XY:
0.0000770
AC XY:
56
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000537
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000522
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.000197
AC:
30
AN:
152322
Hom.:
0
Cov.:
32
AF XY:
0.000255
AC XY:
19
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00118
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.0000675
Hom.:
0
Bravo
AF:
0.000230
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000906
AC:
11
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000237

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 GeneticsAug 12, 2021The c.614G>A (p.S205N) alteration is located in exon 6 (coding exon 5) of the FGGY gene. This alteration results from a G to A substitution at nucleotide position 614, causing the serine (S) at amino acid position 205 to be replaced by an asparagine (N). 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
0.10
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.021
.;T;.
Eigen
Benign
0.13
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.88
D;D;D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.29
T;T;T
MetaSVM
Benign
-0.79
T
MutationAssessor
Uncertain
2.0
M;M;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-1.1
N;N;N
REVEL
Benign
0.088
Sift
Benign
0.12
T;T;T
Sift4G
Benign
0.18
T;T;T
Polyphen
0.20
B;B;.
Vest4
0.60
MVP
0.20
MPC
0.12
ClinPred
0.12
T
GERP RS
5.2
Varity_R
0.42
gMVP
0.64

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: rs376744089; hg19: chr1-59922692; API