Menu
GeneBe

rs369055649

chr2-69329393-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7

The NM_001244710.2(GFPT1):c.1629C>T(p.Asp543=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,610,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

GFPT1
NM_001244710.2 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.0850
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 Likely_benign. Variant got -2 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-69329393-G-A is Benign according to our data. Variant chr2-69329393-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 435320.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.085 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GFPT1NM_001244710.2 linkuse as main transcriptc.1629C>T p.Asp543= synonymous_variant 17/20 ENST00000357308.9
GFPT1NM_002056.4 linkuse as main transcriptc.1575C>T p.Asp525= synonymous_variant 16/19
GFPT1XM_017003801.2 linkuse as main transcriptc.1704C>T p.Asp568= synonymous_variant 17/20
GFPT1XM_017003802.3 linkuse as main transcriptc.1650C>T p.Asp550= synonymous_variant 16/19

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GFPT1ENST00000357308.9 linkuse as main transcriptc.1629C>T p.Asp543= synonymous_variant 17/205 NM_001244710.2 Q06210-1
GFPT1ENST00000361060.5 linkuse as main transcriptc.1575C>T p.Asp525= synonymous_variant 16/191 P1Q06210-2
GFPT1ENST00000674507.1 linkuse as main transcriptc.1575C>T p.Asp525= synonymous_variant 16/18
GFPT1ENST00000674438.1 linkuse as main transcriptc.1359C>T p.Asp453= synonymous_variant 14/17

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000204
AC:
31
AN:
152122
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000676
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000677
AC:
17
AN:
251146
Hom.:
0
AF XY:
0.0000516
AC XY:
7
AN XY:
135736
show subpopulations
Gnomad AFR exome
AF:
0.000554
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000288
AC:
42
AN:
1457804
Hom.:
0
Cov.:
29
AF XY:
0.0000262
AC XY:
19
AN XY:
725470
show subpopulations
Gnomad4 AFR exome
AF:
0.000539
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000128
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000812
Gnomad4 OTH exome
AF:
0.0000498
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000204
AC:
31
AN:
152240
Hom.:
0
Cov.:
32
AF XY:
0.000215
AC XY:
16
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.000674
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000986
Hom.:
0
Bravo
AF:
0.000170

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoNov 11, 2015- -
Congenital myasthenic syndrome 12 Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJul 17, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
Cadd
Benign
11
Dann
Benign
0.53
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs369055649; hg19: chr2-69556525; COSMIC: COSV61947170; API