rs112682152

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001244710.2(GFPT1):c.408+7A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,502,278 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 30 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 32 hom. )

Consequence

GFPT1
NM_001244710.2 splice_region, intron

Scores

Splicing: ADA: 0.0003589

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.491

Publications

0 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 2-69359261-T-A is Benign according to our data. Variant chr2-69359261-T-A is described in ClinVar as Benign. ClinVar VariationId is 257668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0114 (1737/152288) while in subpopulation AFR AF = 0.0395 (1641/41560). AF 95% confidence interval is 0.0379. There are 30 homozygotes in GnomAd4. There are 799 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GFPT1	NM_001244710.2 link	c.408+7A>T	splice_region_variant, intron_variant	Intron 5 of 19	ENST00000357308.9	NP_001231639.1	Q06210-1
GFPT1	NM_002056.4 link	c.408+7A>T	splice_region_variant, intron_variant	Intron 5 of 18		NP_002047.2	Q06210-2
GFPT1	XM_017003801.2 link	c.483+7A>T	splice_region_variant, intron_variant	Intron 5 of 19		XP_016859290.1
GFPT1	XM_017003802.3 link	c.483+7A>T	splice_region_variant, intron_variant	Intron 5 of 18		XP_016859291.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GFPT1	ENST00000357308.9 link	c.408+7A>T	splice_region_variant, intron_variant	Intron 5 of 19	5	NM_001244710.2	ENSP00000349860.4	Q06210-1
GFPT1	ENST00000361060.5 link	c.408+7A>T	splice_region_variant, intron_variant	Intron 5 of 18	1		ENSP00000354347.4	Q06210-2
GFPT1	ENST00000674507.1 link	c.408+7A>T	splice_region_variant, intron_variant	Intron 5 of 17			ENSP00000501332.1	A0A6I8PTT9
GFPT1	ENST00000674438.1 link	c.192+7A>T	splice_region_variant, intron_variant	Intron 3 of 16			ENSP00000501469.1	A0A6I8PRN4

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1731

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0395

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00400

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00766

GnomAD2 exomes

AF:

0.00309

AC:

775

AN:

251144

AF XY:

0.00224

show subpopulations

Gnomad AFR exome

AF:

0.0430

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00114

AC:

1543

AN:

1349990

Hom.:

Cov.:

AF XY:

0.000949

AC XY:

643

AN XY:

677872

show subpopulations

African (AFR)

AF:

0.0407

AC:

1275

AN:

31298

American (AMR)

AF:

0.00175

AC:

AN:

44570

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25452

East Asian (EAS)

AF:

0.00

AC:

AN:

39174

South Asian (SAS)

AF:

0.000107

AC:

AN:

83952

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53336

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

4948

European-Non Finnish (NFE)

AF:

0.0000237

AC:

AN:

1010680

Other (OTH)

AF:

0.00256

AC:

145

AN:

56580

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

127

190

254

317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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:

0.0114

AC:

1737

AN:

152288

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

799

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.0395

AC:

1641

AN:

41560

American (AMR)

AF:

0.00399

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68032

Other (OTH)

AF:

0.00758

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

169

253

338

422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00366

Hom.:

Bravo

AF:

0.0135

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 07, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Congenital myasthenic syndrome 12

Benign:2

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. -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

9.0

(source)

DANN

Benign

0.68

PhyloP100

0.49

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00036

dbscSNV1_RF

Benign

0.014

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

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