2-69326167-G-C

Variant names:

• chr2-69326167-G-C
• rs199678034
• NM_001244710.2:c.*22C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001244710.2(GFPT1):​c.*22C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000397 in 1,511,352 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: GFPT1 NM_001244710.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525
• Publications: 8 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), PanelApp Australia, Ambry Genetics, Illumina
• congenital myasthenic syndromes with glycosylation defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFPT1	NM_001244710.2	MANE Select	c.*22C>G		3_prime_UTR	Exon 20 of 20	NP_001231639.1
	GFPT1	NM_002056.4		c.*22C>G		3_prime_UTR	Exon 19 of 19	NP_002047.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFPT1	ENST00000357308.9	TSL:5 MANE Select	c.*22C>G		3_prime_UTR	Exon 20 of 20	ENSP00000349860.4
	GFPT1	ENST00000361060.5	TSL:1	c.*22C>G		3_prime_UTR	Exon 19 of 19	ENSP00000354347.4
	GFPT1	ENST00000674507.1		c.*22C>G		3_prime_UTR	Exon 18 of 18	ENSP00000501332.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151010 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000488

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000294 AC: 4 AN: 1360342 Hom.: 0 Cov.: 22 AF XY: 0.00000147 AC XY: 1 AN XY: 682422

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000127 AC: 4 AN: 31436

American (AMR) AF: 0.00 AC: 0 AN: 44516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25430

East Asian (EAS) AF: 0.00 AC: 0 AN: 39130

South Asian (SAS) AF: 0.00 AC: 0 AN: 83798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5472

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1021080

Other (OTH) AF: 0.00 AC: 0 AN: 56908

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0126737), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151010 Hom.: 0 Cov.: 32 AF XY: 0.0000272 AC XY: 2 AN XY: 73582

African (AFR) AF: 0.0000488 AC: 2 AN: 41016

American (AMR) AF: 0.00 AC: 0 AN: 15128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67900

Other (OTH) AF: 0.00 AC: 0 AN: 2068

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.14
DANN	Benign	0.55
PhyloP100		0.53

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: rs199678034; hg19: chr2-69553299;