5-180316365-C-A

Variant names:

• chr5-180316365-C-A
• rs368601222
• NM_005110.4:c.1249G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005110.4(GFPT2):​c.1249G>T​(p.Val417Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V417I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: GFPT2 NM_005110.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.07
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.894

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.1249G>T	p.Val417Phe	missense	Exon 13 of 19	NP_005101.1	A0A0S2Z4X9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFPT2	ENST00000253778.13	TSL:1 MANE Select	c.1249G>T	p.Val417Phe	missense	Exon 13 of 19	ENSP00000253778.8	O94808
	GFPT2	ENST00000889627.1		c.1312G>T	p.Val438Phe	missense	Exon 14 of 20	ENSP00000559686.1
	GFPT2	ENST00000920229.1		c.1246G>T	p.Val416Phe	missense	Exon 13 of 19	ENSP00000590288.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 249478 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461810 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727206

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000895 AC: 4 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111952

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.74	D
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	-0.024	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		6.1
PrimateAI	Pathogenic	0.93	D
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.017	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.65		Gain of catalytic residue at V417 (P = 0.0229)
MVP		0.89
MPC		1.3
ClinPred		0.94	D
GERP RS		5.9
Varity_R		0.94
gMVP		0.96
Mutation Taster		=27/73	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs368601222; hg19: chr5-179743365;