chr1-59340041-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018291.5(FGGY):ā€‹c.285G>Cā€‹(p.Gln95His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,612,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q95E) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.000092 ( 0 hom., cov: 32)
Exomes š‘“: 0.00014 ( 0 hom. )

Consequence

FGGY
NM_018291.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.16
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.071029454).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FGGYNM_018291.5 linkuse as main transcriptc.285G>C p.Gln95His missense_variant 3/16 ENST00000303721.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FGGYENST00000303721.12 linkuse as main transcriptc.285G>C p.Gln95His missense_variant 3/161 NM_018291.5 P1Q96C11-1

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
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:
0.000162
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000105
AC:
26
AN:
247166
Hom.:
0
AF XY:
0.0000670
AC XY:
9
AN XY:
134274
show subpopulations
Gnomad AFR exome
AF:
0.000131
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000140
Gnomad NFE exome
AF:
0.000187
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000138
AC:
202
AN:
1460626
Hom.:
0
Cov.:
30
AF XY:
0.000121
AC XY:
88
AN XY:
726502
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.000175
Gnomad4 OTH exome
AF:
0.0000829
GnomAD4 genome
AF:
0.0000919
AC:
14
AN:
152284
Hom.:
0
Cov.:
32
AF XY:
0.0000806
AC XY:
6
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000675
Hom.:
0
Bravo
AF:
0.0000718
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000279
AC:
2
ExAC
AF:
0.000108
AC:
13
EpiCase
AF:
0.000273
EpiControl
AF:
0.000238

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 GeneticsOct 20, 2023The c.285G>C (p.Q95H) alteration is located in exon 3 (coding exon 2) of the FGGY gene. This alteration results from a G to C substitution at nucleotide position 285, causing the glutamine (Q) at amino acid position 95 to be replaced by a histidine (H). 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
0.11
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
15
DANN
Uncertain
1.0
DEOGEN2
Benign
0.013
T;.;T
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.18
FATHMM_MKL
Benign
0.75
D
LIST_S2
Benign
0.83
T;T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.071
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
.;L;L
MutationTaster
Benign
0.67
D;D;D
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-1.7
N;N;N
REVEL
Benign
0.031
Sift
Benign
0.15
T;T;T
Sift4G
Benign
0.11
T;T;T
Polyphen
0.72, 0.014
.;P;B
Vest4
0.33, 0.32
MutPred
0.43
Loss of stability (P = 0.1116);Loss of stability (P = 0.1116);Loss of stability (P = 0.1116);
MVP
0.29
MPC
0.025
ClinPred
0.085
T
GERP RS
1.2
Varity_R
0.092
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs184449304; hg19: chr1-59805713; API