rs6720415

Variant names:

• chr2-69387029-A-G
• rs6720415
• NM_001244710.2:c.7+36T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-69387029-A-G
• chr2-69387029-A-C
• chr2-69387029-A-T

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.7+36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 1,484,594 control chromosomes in the GnomAD database, including 266,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (34472 hom., cov: 34)
  • Exomes 𝑓: 0.59 (231613 hom.)
• Consequence: GFPT1 NM_001244710.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.280
• Publications: 13 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=-0.54).
• BP6: Variant 2-69387029-A-G is Benign according to our data. Variant chr2-69387029-A-G is described in ClinVar as Benign. ClinVar VariationId is 258544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 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.7+36T>C		intron	N/A	NP_001231639.1	Q06210-1
	GFPT1	NM_002056.4		c.7+36T>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.7+36T>C		intron	N/A	ENSP00000349860.4	Q06210-1
	GFPT1	ENST00000361060.5	TSL:1	c.7+36T>C		intron	N/A	ENSP00000354347.4	Q06210-2
	GFPT1	ENST00000955842.1		c.7+36T>C		intron	N/A	ENSP00000625901.1

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100169 AN: 151978 Hom.: 34431 Cov.: 34

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.628

GnomAD2 exomes AF: 0.574 AC: 74642 AN: 129932 AF XY: 0.577

Gnomad AFR exome AF: 0.858

Gnomad AMR exome AF: 0.501

Gnomad ASJ exome AF: 0.666

Gnomad EAS exome AF: 0.455

Gnomad FIN exome AF: 0.580

Gnomad NFE exome AF: 0.575

Gnomad OTH exome AF: 0.582

GnomAD4 exome AF: 0.587 AC: 781747 AN: 1332502 Hom.: 231613 Cov.: 24 AF XY: 0.587 AC XY: 387819 AN XY: 660692

African (AFR) AF: 0.876 AC: 25921 AN: 29588

American (AMR) AF: 0.510 AC: 18323 AN: 35902

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 16347 AN: 24626

East Asian (EAS) AF: 0.454 AC: 15919 AN: 35080

South Asian (SAS) AF: 0.609 AC: 47580 AN: 78164

European-Finnish (FIN) AF: 0.573 AC: 20127 AN: 35118

Middle Eastern (MID) AF: 0.589 AC: 3272 AN: 5558

European-Non Finnish (NFE) AF: 0.582 AC: 600662 AN: 1032414

Other (OTH) AF: 0.599 AC: 33596 AN: 56052

GnomAD4 genome AF: 0.659 AC: 100262 AN: 152092 Hom.: 34472 Cov.: 34 AF XY: 0.655 AC XY: 48699 AN XY: 74342

African (AFR) AF: 0.869 AC: 36097 AN: 41538

American (AMR) AF: 0.570 AC: 8722 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2207 AN: 3470

East Asian (EAS) AF: 0.469 AC: 2415 AN: 5150

South Asian (SAS) AF: 0.620 AC: 2996 AN: 4832

European-Finnish (FIN) AF: 0.577 AC: 6092 AN: 10558

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.583 AC: 39608 AN: 67940

Other (OTH) AF: 0.633 AC: 1339 AN: 2114

Alfa AF: 0.563 Hom.: 3294

Bravo AF: 0.666

Asia WGS AF: 0.593 AC: 2061 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.73
PhyloP100		0.28
PromoterAI		-0.0098	Neutral
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.3
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: rs6720415; hg19: chr2-69614161; COSMIC: COSV61951263;