rs199678034

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-69326167-G-A
• chr2-69326167-G-C
• chr2-69326167-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001244710.2(GFPT1):​c.*22C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000265 in 1,511,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: GFPT1 NM_001244710.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GFPT1	NM_001244710.2	c.*22C>T		3_prime_UTR_variant	Exon 20 of 20	ENST00000357308.9	NP_001231639.1
GFPT1	NM_002056.4	c.*22C>T		3_prime_UTR_variant	Exon 19 of 19		NP_002047.2
GFPT1	XM_017003801.2	c.*22C>T		3_prime_UTR_variant	Exon 20 of 20		XP_016859290.1
GFPT1	XM_017003802.3	c.*22C>T		3_prime_UTR_variant	Exon 19 of 19		XP_016859291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GFPT1	ENST00000357308.9	c.*22C>T		3_prime_UTR_variant	Exon 20 of 20	5	NM_001244710.2	ENSP00000349860.4
GFPT1	ENST00000361060.5	c.*22C>T		3_prime_UTR_variant	Exon 19 of 19	1		ENSP00000354347.4
GFPT1	ENST00000674507.1	c.*22C>T		3_prime_UTR_variant	Exon 18 of 18			ENSP00000501332.1
GFPT1	ENST00000674438.1	c.*22C>T		3_prime_UTR_variant	Exon 17 of 17			ENSP00000501469.1

Frequencies

GnomAD3 genomes AF: 0.000113 AC: 17 AN: 151010 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000488

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000925

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 249944 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

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: 0.0000169 AC: 23 AN: 1360342 Hom.: 0 Cov.: 22 AF XY: 0.0000132 AC XY: 9 AN XY: 682422

African (AFR) AF: 0.00 AC: 0 AN: 31436

American (AMR) AF: 0.000247 AC: 11 AN: 44516

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

East Asian (EAS) AF: 0.0000256 AC: 1 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: 0.00000588 AC: 6 AN: 1021080

Other (OTH) AF: 0.0000879 AC: 5 AN: 56908

GnomAD4 genome AF: 0.000112 AC: 17 AN: 151126 Hom.: 0 Cov.: 32 AF XY: 0.0000950 AC XY: 7 AN XY: 73708

African (AFR) AF: 0.0000486 AC: 2 AN: 41138

American (AMR) AF: 0.000924 AC: 14 AN: 15148

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67892

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000219

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital myasthenic syndrome 12 Uncertain:1

Jul 30, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant occurs in a non-coding region of the GFPT1 gene. It does not change the encoded amino acid sequence of the GFPT1 protein. This variant is present in population databases (rs199678034, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with GFPT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1505977). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.29
DANN	Benign	0.62
PhyloP100		0.53

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: rs199678034; hg19: chr2-69553299;