chr1-74201361-G-C

Variant summary

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

The NM_003838.5(FPGT):ā€‹c.294G>Cā€‹(p.Lys98Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,611,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.000025 ( 0 hom. )

Consequence

FPGT
NM_003838.5 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.451
Variant links:
Genes affected
FPGT (HGNC:3825): (fucose-1-phosphate guanylyltransferase) L-fucose is a key sugar in glycoproteins and other complex carbohydrates since it may be involved in many of the functional roles of these macromolecules, such as in cell-cell recognition. The fucosyl donor for these fucosylated oligosaccharides is GDP-beta-L-fucose. There are two alternate pathways for the biosynthesis of GDP-fucose; the major pathway converts GDP-alpha-D-mannose to GDP-beta-L-fucose. The protein encoded by this gene participates in an alternate pathway that is present in certain mammalian tissues, such as liver and kidney, and appears to function as a salvage pathway to reutilize L-fucose arising from the turnover of glycoproteins and glycolipids. This pathway involves the phosphorylation of L-fucose to form beta-L-fucose-1-phosphate, and then condensation of the beta-L-fucose-1-phosphate with GTP by fucose-1-phosphate guanylyltransferase to form GDP-beta-L-fucose. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream TNNI3 interacting kinase (TNNI3K) gene. [provided by RefSeq, Dec 2010]

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=0.08065975).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FPGTNM_003838.5 linkuse as main transcriptc.294G>C p.Lys98Asn missense_variant 3/4 ENST00000370898.9
FPGT-TNNI3KNM_001112808.3 linkuse as main transcriptc.294G>C p.Lys98Asn missense_variant 3/27

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FPGTENST00000370898.9 linkuse as main transcriptc.294G>C p.Lys98Asn missense_variant 3/41 NM_003838.5 P1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152132
Hom.:
0
Cov.:
33
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000404
AC:
1
AN:
247502
Hom.:
0
AF XY:
0.00000746
AC XY:
1
AN XY:
134052
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000902
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000253
AC:
37
AN:
1459620
Hom.:
0
Cov.:
29
AF XY:
0.0000234
AC XY:
17
AN XY:
726182
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:
0.00
Gnomad4 NFE exome
AF:
0.0000333
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152132
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151

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 GeneticsSep 14, 2023The c.294G>C (p.K98N) alteration is located in exon 3 (coding exon 3) of the FPGT gene. This alteration results from a G to C substitution at nucleotide position 294, causing the lysine (K) at amino acid position 98 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
0.094
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
13
DANN
Uncertain
0.98
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.58
FATHMM_MKL
Benign
0.080
N
LIST_S2
Benign
0.71
T;T;T;T;T;T;T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.081
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
2.0
.;M;M;.;.;.;.;.;.
MutationTaster
Benign
1.0
N;N;N;N;N;N;N;N
PROVEAN
Benign
-1.2
.;N;N;N;.;N;N;N;N
REVEL
Benign
0.032
Sift
Benign
0.15
.;T;T;T;.;T;T;T;T
Sift4G
Benign
0.32
T;T;T;T;T;T;T;T;T
Vest4
0.12
MutPred
0.35
.;Loss of ubiquitination at K98 (P = 0.0192);Loss of ubiquitination at K98 (P = 0.0192);.;.;Loss of ubiquitination at K98 (P = 0.0192);Loss of ubiquitination at K98 (P = 0.0192);Loss of ubiquitination at K98 (P = 0.0192);Loss of ubiquitination at K98 (P = 0.0192);
MVP
0.64
MPC
0.024
ClinPred
0.18
T
GERP RS
0.040
Varity_R
0.046
gMVP
0.23

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: rs199983332; hg19: chr1-74667045; API