rs1553386276

Variant summary

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

The NM_001244710.2(GFPT1):​c.1534G>A​(p.Asp512Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

GFPT1
NM_001244710.2 missense

Scores

3
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.81
Variant links:
Genes affected
GFPT1 (HGNC:4241): (glutamine--fructose-6-phosphate transaminase 1) This gene encodes the first and rate-limiting enzyme of the hexosamine pathway and controls the flux of glucose into the hexosamine pathway. The product of this gene catalyzes the formation of glucosamine 6-phosphate. [provided by RefSeq, Sep 2008]

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=0.35787597).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GFPT1NM_001244710.2 linkc.1534G>A p.Asp512Asn missense_variant 16/20 ENST00000357308.9 NP_001231639.1 Q06210-1
GFPT1NM_002056.4 linkc.1480G>A p.Asp494Asn missense_variant 15/19 NP_002047.2 Q06210-2
GFPT1XM_017003801.2 linkc.1609G>A p.Asp537Asn missense_variant 16/20 XP_016859290.1
GFPT1XM_017003802.3 linkc.1555G>A p.Asp519Asn missense_variant 15/19 XP_016859291.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GFPT1ENST00000357308.9 linkc.1534G>A p.Asp512Asn missense_variant 16/205 NM_001244710.2 ENSP00000349860.4 Q06210-1
GFPT1ENST00000361060.5 linkc.1480G>A p.Asp494Asn missense_variant 15/191 ENSP00000354347.4 Q06210-2
GFPT1ENST00000674507.1 linkc.1480G>A p.Asp494Asn missense_variant 15/18 ENSP00000501332.1 A0A6I8PTT9
GFPT1ENST00000674438.1 linkc.1264G>A p.Asp422Asn missense_variant 13/17 ENSP00000501469.1 A0A6I8PRN4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

Congenital myasthenic syndrome 12 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpSep 07, 2022ClinVar contains an entry for this variant (Variation ID: 473128). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with GFPT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 494 of the GFPT1 protein (p.Asp494Asn). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.072
T
BayesDel_noAF
Benign
-0.34
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.67
D;.
Eigen
Uncertain
0.28
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.97
D;D
M_CAP
Benign
0.048
D
MetaRNN
Benign
0.36
T;T
MetaSVM
Benign
-0.65
T
MutationAssessor
Benign
1.3
L;.
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-2.3
N;N
REVEL
Benign
0.16
Sift
Benign
0.065
T;T
Sift4G
Benign
0.14
T;T
Polyphen
0.43
.;B
Vest4
0.48
MutPred
0.32
Gain of MoRF binding (P = 0.0584);.;
MVP
0.75
MPC
1.3
ClinPred
0.93
D
GERP RS
5.3
RBP_binding_hub_radar
1.0
RBP_regulation_power_radar
2.8
Varity_R
0.39
gMVP
0.88

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: rs1553386276; hg19: chr2-69556879; API