dbSNP rs369055649: GFPT1:p.Asp543Asp (chr2-69329393-G-A) – ACMG Classification: Likely_benign (-2 pts)

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.Asp543Asp) 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

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]

GFPT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

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

Synonymous conserved (PhyloP=-0.085 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GFPT1	NM_001244710.2 link	c.1629C>T	p.Asp543Asp	synonymous_variant	Exon 17 of 20	ENST00000357308.9	NP_001231639.1	Q06210-1
GFPT1	NM_002056.4 link	c.1575C>T	p.Asp525Asp	synonymous_variant	Exon 16 of 19		NP_002047.2	Q06210-2
GFPT1	XM_017003801.2 link	c.1704C>T	p.Asp568Asp	synonymous_variant	Exon 17 of 20		XP_016859290.1
GFPT1	XM_017003802.3 link	c.1650C>T	p.Asp550Asp	synonymous_variant	Exon 16 of 19		XP_016859291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GFPT1	ENST00000357308.9 link	c.1629C>T	p.Asp543Asp	synonymous_variant	Exon 17 of 20	5	NM_001244710.2	ENSP00000349860.4	Q06210-1
GFPT1	ENST00000361060.5 link	c.1575C>T	p.Asp525Asp	synonymous_variant	Exon 16 of 19	1		ENSP00000354347.4	Q06210-2
GFPT1	ENST00000674507.1 link	c.1575C>T	p.Asp525Asp	synonymous_variant	Exon 16 of 18			ENSP00000501332.1	A0A6I8PTT9
GFPT1	ENST00000674438.1 link	c.1359C>T	p.Asp453Asp	synonymous_variant	Exon 14 of 17			ENSP00000501469.1	A0A6I8PRN4

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152122

Hom.:

Cov.:

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:

AN:

251146

Hom.:

AF XY:

0.0000516

AC XY:

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:

AN:

1457804

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

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

AF:

0.000204

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

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.:

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

Nov 11, 2015

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital myasthenic syndrome 12

Benign:1

Apr 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over