2-69369060-T-C

Variant names:

• chr2-69369060-T-C
• rs13419122
• NM_001244710.2:c.223+941A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001244710.2(GFPT1):​c.223+941A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,060 control chromosomes in the GnomAD database, including 34,122 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 0.66 (34122 hom., cov: 32)
• Consequence: GFPT1 NM_001244710.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 12

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Illumina
• congenital myasthenic syndromes with glycosylation defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001244710.2. 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
	GFPT1	NM_001244710.2	MANE Select	c.223+941A>G		intron	N/A	NP_001231639.1	Q06210-1
	GFPT1	NM_002056.4		c.223+941A>G		intron	N/A	NP_002047.2	Q06210-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFPT1	ENST00000357308.9	TSL:5 MANE Select	c.223+941A>G		intron	N/A	ENSP00000349860.4	Q06210-1
	GFPT1	ENST00000361060.5	TSL:1	c.223+941A>G		intron	N/A	ENSP00000354347.4	Q06210-2
	GFPT1	ENST00000955842.1		c.223+941A>G		intron	N/A	ENSP00000625901.1

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99727 AN: 151942 Hom.: 34081 Cov.: 32

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.627

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.656 AC: 99821 AN: 152060 Hom.: 34122 Cov.: 32 AF XY: 0.652 AC XY: 48483 AN XY: 74348

African (AFR) AF: 0.861 AC: 35708 AN: 41486

American (AMR) AF: 0.567 AC: 8654 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2215 AN: 3472

East Asian (EAS) AF: 0.467 AC: 2410 AN: 5164

South Asian (SAS) AF: 0.620 AC: 2989 AN: 4818

European-Finnish (FIN) AF: 0.576 AC: 6096 AN: 10582

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39624 AN: 67956

Other (OTH) AF: 0.632 AC: 1337 AN: 2116

Alfa AF: 0.578 Hom.: 2680

Bravo AF: 0.663

Asia WGS AF: 0.593 AC: 2063 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.6
DANN	Benign	0.74
PhyloP100		-0.041
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13419122; hg19: chr2-69596192;