chr5-180336290-G-A

Position:

• chr5-180336290-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005110.4(GFPT2):​c.214+189C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 619,910 control chromosomes in the GnomAD database, including 8,886 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1740 hom., cov: 33)
  • Exomes 𝑓: 0.17 (7146 hom.)
• Consequence: GFPT2 NM_005110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GFPT2	NM_005110.4	c.214+189C>T		intron_variant		ENST00000253778.13	NP_005101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GFPT2	ENST00000253778.13	c.214+189C>T		intron_variant		1	NM_005110.4	ENSP00000253778	P1
GFPT2	ENST00000503546.1	n.522C>T		non_coding_transcript_exon_variant	3/3	2
GFPT2	ENST00000518158.5	n.333+189C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20760 AN: 151944 Hom.: 1740 Cov.: 33

Gnomad AFR AF: 0.0452

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.171 AC: 79869 AN: 467846 Hom.: 7146 Cov.: 3 AF XY: 0.169 AC XY: 42064 AN XY: 248374

Gnomad4 AFR exome AF: 0.0434

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.194

Gnomad4 SAS exome AF: 0.122

Gnomad4 FIN exome AF: 0.175

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.166

GnomAD4 genome AF: 0.136 AC: 20754 AN: 152064 Hom.: 1740 Cov.: 33 AF XY: 0.135 AC XY: 10025 AN XY: 74326

Gnomad4 AFR AF: 0.0450

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.138

Alfa AF: 0.148 Hom.: 235

Bravo AF: 0.128

Asia WGS AF: 0.155 AC: 536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.2
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs6864729; hg19: chr5-179763290;