Genetic Variant NM_005110.4:c.1358G>A (chr5-180313880-C-T) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_005110.4(GFPT2):c.1358G>A(p.Ser453Asn) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S453G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GFPT2
NM_005110.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.61

Publications

0 publications found

Variant links:

Genes affected

GFPT2 (HGNC:4242): (glutamine-fructose-6-phosphate transaminase 2) Predicted to enable glutamine-fructose-6-phosphate transaminase (isomerizing) activity. Predicted to be involved in UDP-N-acetylglucosamine metabolic process; fructose 6-phosphate metabolic process; and protein N-linked glycosylation. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Predicted to be located in cytosol. Implicated in type 2 diabetes mellitus. [provided by Alliance of Genome Resources, Apr 2022]

GFPT2 links:

ENSG00000297119 (HGNC:):

ENSG00000297119 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.973

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005110.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFPT2	NM_005110.4	MANE Select	c.1358G>A	p.Ser453Asn	missense	Exon 14 of 19	NP_005101.1	A0A0S2Z4X9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GFPT2	ENST00000253778.13	TSL:1 MANE Select	c.1358G>A	p.Ser453Asn	missense	Exon 14 of 19	ENSP00000253778.8	O94808
GFPT2	ENST00000889627.1		c.1421G>A	p.Ser474Asn	missense	Exon 15 of 20	ENSP00000559686.1
GFPT2	ENST00000920229.1		c.1355G>A	p.Ser452Asn	missense	Exon 14 of 19	ENSP00000590288.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1454046

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723584

African (AFR)

AF:

0.00

AC:

AN:

33380

American (AMR)

AF:

0.00

AC:

AN:

44568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26066

East Asian (EAS)

AF:

0.00

AC:

AN:

39648

South Asian (SAS)

AF:

0.00

AC:

AN:

85726

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47958

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5454

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111084

Other (OTH)

AF:

0.00

AC:

AN:

60162

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.84

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.93

FATHMM_MKL

Benign

0.62

LIST_S2

Pathogenic

1.0

M_CAP

Uncertain

0.22

MetaRNN

Pathogenic

0.97

MetaSVM

Pathogenic

0.80

MutationAssessor

Pathogenic

4.4

PhyloP100

7.6

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.7

REVEL

Pathogenic

0.76

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.89

MutPred

0.90

Loss of disorder (P = 0.086)

MVP

0.96

MPC

1.1

ClinPred

1.0

GERP RS

5.8

Varity_R

0.90

gMVP

0.99

Mutation Taster

=29/71

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over