rs78952091

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001244710.2(GFPT1):c.675C>T(p.Leu225Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,584,282 control chromosomes in the GnomAD database, including 1,385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 128 hom., cov: 33)

Exomes 𝑓: 0.014 ( 1257 hom. )

Consequence

GFPT1
NM_001244710.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.33

Publications

10 publications found

Variant links:

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

GFPT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 2-69354499-G-A is Benign according to our data. Variant chr2-69354499-G-A is described in ClinVar as Benign. ClinVar VariationId is 129153.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
GFPT1	NM_001244710.2 link	c.675C>T	p.Leu225Leu	synonymous_variant	Exon 8 of 20	ENST00000357308.9	NP_001231639.1
GFPT1	NM_002056.4 link	c.675C>T	p.Leu225Leu	synonymous_variant	Exon 8 of 19		NP_002047.2
GFPT1	XM_017003801.2 link	c.750C>T	p.Leu250Leu	synonymous_variant	Exon 8 of 20		XP_016859290.1
GFPT1	XM_017003802.3 link	c.750C>T	p.Leu250Leu	synonymous_variant	Exon 8 of 19		XP_016859291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
GFPT1	ENST00000357308.9 link	c.675C>T	p.Leu225Leu	synonymous_variant	Exon 8 of 20	5	NM_001244710.2	ENSP00000349860.4
GFPT1	ENST00000361060.5 link	c.675C>T	p.Leu225Leu	synonymous_variant	Exon 8 of 19	1		ENSP00000354347.4
GFPT1	ENST00000674507.1 link	c.675C>T	p.Leu225Leu	synonymous_variant	Exon 8 of 18			ENSP00000501332.1
GFPT1	ENST00000674438.1 link	c.459C>T	p.Leu153Leu	synonymous_variant	Exon 6 of 17			ENSP00000501469.1

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2237

AN:

152092

Hom.:

128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00498

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.184

Gnomad SAS

AF:

0.0981

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00232

Gnomad OTH

AF:

0.0168

GnomAD2 exomes

AF:

0.0285

AC:

7152

AN:

251134

AF XY:

0.0306

show subpopulations

Gnomad AFR exome

AF:

0.0138

Gnomad AMR exome

AF:

0.00173

Gnomad ASJ exome

AF:

0.00516

Gnomad EAS exome

AF:

0.186

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.00208

Gnomad OTH exome

AF:

0.0145

GnomAD4 exome

AF:

0.0137

AC:

19607

AN:

1432072

Hom.:

1257

Cov.:

AF XY:

0.0160

AC XY:

11420

AN XY:

714372

show subpopulations

African (AFR)

AF:

0.0135

AC:

443

AN:

32920

American (AMR)

AF:

0.00186

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00505

AC:

131

AN:

25932

East Asian (EAS)

AF:

0.188

AC:

7417

AN:

39494

South Asian (SAS)

AF:

0.0937

AC:

8019

AN:

85600

European-Finnish (FIN)

AF:

0.000731

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.00947

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00198

AC:

2145

AN:

1085052

Other (OTH)

AF:

0.0215

AC:

1276

AN:

59306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

945

1891

2836

3782

4727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

282

564

846

1128

1410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0147

AC:

2234

AN:

152210

Hom.:

128

Cov.:

AF XY:

0.0169

AC XY:

1259

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0127

AC:

526

AN:

41520

American (AMR)

AF:

0.00497

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

AN:

3472

East Asian (EAS)

AF:

0.184

AC:

952

AN:

5178

South Asian (SAS)

AF:

0.0971

AC:

468

AN:

4818

European-Finnish (FIN)

AF:

0.000378

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00232

AC:

158

AN:

68036

Other (OTH)

AF:

0.0166

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

102

205

307

410

512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00525

Hom.:

Bravo

AF:

0.0140

Asia WGS

AF:

0.127

AC:

442

AN:

3478

EpiCase

AF:

0.00229

EpiControl

AF:

0.00267

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Oct 18, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Congenital myasthenic syndrome 12

Benign:2

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

1.5

(source)

DANN

Benign

0.70

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.24

Position offset: -10

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over