chr2-69359238-A-G

Variant names:

• chr2-69359238-A-G
• rs67760762
• NM_001244710.2:c.408+30T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001244710.2(GFPT1):​c.408+30T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,216,722 control chromosomes in the GnomAD database, including 93,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (9054 hom., cov: 32)
  • Exomes 𝑓: 0.39 (84467 hom.)
• Consequence: GFPT1 NM_001244710.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.553
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-69359238-A-G is Benign according to our data. Variant chr2-69359238-A-G is described in ClinVar as Benign. ClinVar VariationId is 258543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.413 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.408+30T>C		intron	N/A	NP_001231639.1	Q06210-1
	GFPT1	NM_002056.4		c.408+30T>C		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.408+30T>C		intron	N/A	ENSP00000349860.4	Q06210-1
	GFPT1	ENST00000361060.5	TSL:1	c.408+30T>C		intron	N/A	ENSP00000354347.4	Q06210-2
	GFPT1	ENST00000955842.1		c.456+30T>C		intron	N/A	ENSP00000625901.1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47295 AN: 151960 Hom.: 9042 Cov.: 32

Gnomad AFR AF: 0.0850

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.352

GnomAD2 exomes AF: 0.370 AC: 92875 AN: 250888 AF XY: 0.375

Gnomad AFR exome AF: 0.0745

Gnomad AMR exome AF: 0.385

Gnomad ASJ exome AF: 0.551

Gnomad EAS exome AF: 0.215

Gnomad FIN exome AF: 0.383

Gnomad NFE exome AF: 0.424

Gnomad OTH exome AF: 0.408

GnomAD4 exome AF: 0.389 AC: 413765 AN: 1064642 Hom.: 84467 Cov.: 15 AF XY: 0.389 AC XY: 213123 AN XY: 548196

African (AFR) AF: 0.0706 AC: 1830 AN: 25920

American (AMR) AF: 0.384 AC: 16964 AN: 44180

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 12983 AN: 23632

East Asian (EAS) AF: 0.196 AC: 7411 AN: 37880

South Asian (SAS) AF: 0.332 AC: 25974 AN: 78234

European-Finnish (FIN) AF: 0.383 AC: 20363 AN: 53126

Middle Eastern (MID) AF: 0.397 AC: 1813 AN: 4568

European-Non Finnish (NFE) AF: 0.411 AC: 308334 AN: 749780

Other (OTH) AF: 0.382 AC: 18093 AN: 47322

GnomAD4 genome AF: 0.311 AC: 47313 AN: 152080 Hom.: 9054 Cov.: 32 AF XY: 0.311 AC XY: 23121 AN XY: 74310

African (AFR) AF: 0.0848 AC: 3521 AN: 41526

American (AMR) AF: 0.372 AC: 5670 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1839 AN: 3466

East Asian (EAS) AF: 0.200 AC: 1035 AN: 5174

South Asian (SAS) AF: 0.338 AC: 1631 AN: 4828

European-Finnish (FIN) AF: 0.374 AC: 3942 AN: 10546

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28349 AN: 67970

Other (OTH) AF: 0.360 AC: 758 AN: 2106

Alfa AF: 0.326 Hom.: 1609

Bravo AF: 0.301

Asia WGS AF: 0.288 AC: 1001 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Congenital myasthenic syndrome 12 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.67
PhyloP100		-0.55
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		2.0
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: rs67760762; hg19: chr2-69586370; COSMIC: COSV61946580; COSMIC: COSV61946580;