2-69345897-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001244710.2(GFPT1):c.1105+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,363,988 control chromosomes in the GnomAD database, including 238,445 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 0.65 ( 33607 hom., cov: 32)

Exomes 𝑓: 0.58 ( 204838 hom. )

Consequence

GFPT1
NM_001244710.2 splice_region, intron

Scores

Splicing: ADA: 0.004978

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 2.45

Publications

17 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=-0.69).

BP6

Variant 2-69345897-T-C is Benign according to our data. Variant chr2-69345897-T-C is described in ClinVar as Benign. ClinVar VariationId is 129151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
GFPT1	NM_001244710.2 link	c.1105+7A>G	splice_region_variant, intron_variant	Intron 12 of 19	ENST00000357308.9	NP_001231639.1
GFPT1	NM_002056.4 link	c.1051+7A>G	splice_region_variant, intron_variant	Intron 11 of 18		NP_002047.2
GFPT1	XM_017003801.2 link	c.1180+7A>G	splice_region_variant, intron_variant	Intron 12 of 19		XP_016859290.1
GFPT1	XM_017003802.3 link	c.1126+7A>G	splice_region_variant, intron_variant	Intron 11 of 18		XP_016859291.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
GFPT1	ENST00000357308.9 link	c.1105+7A>G	splice_region_variant, intron_variant	Intron 12 of 19	5	NM_001244710.2	ENSP00000349860.4
GFPT1	ENST00000361060.5 link	c.1051+7A>G	splice_region_variant, intron_variant	Intron 11 of 18	1		ENSP00000354347.4
GFPT1	ENST00000674507.1 link	c.1051+7A>G	splice_region_variant, intron_variant	Intron 11 of 17			ENSP00000501332.1
GFPT1	ENST00000674438.1 link	c.835+7A>G	splice_region_variant, intron_variant	Intron 9 of 16			ENSP00000501469.1

Frequencies

GnomAD3 genomes

AF:

0.652

AC:

99056

AN:

151972

Hom.:

33568

Cov.:

show subpopulations

Gnomad AFR

AF:

0.850

Gnomad AMI

AF:

0.667

Gnomad AMR

AF:

0.566

Gnomad ASJ

AF:

0.646

Gnomad EAS

AF:

0.468

Gnomad SAS

AF:

0.622

Gnomad FIN

AF:

0.556

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.582

Gnomad OTH

AF:

0.625

GnomAD2 exomes

AF:

0.587

AC:

147155

AN:

250732

AF XY:

0.587

show subpopulations

Gnomad AFR exome

AF:

0.856

Gnomad AMR exome

AF:

0.497

Gnomad ASJ exome

AF:

0.675

Gnomad EAS exome

AF:

0.469

Gnomad FIN exome

AF:

0.559

Gnomad NFE exome

AF:

0.585

Gnomad OTH exome

AF:

0.581

GnomAD4 exome

AF:

0.578

AC:

700337

AN:

1211898

Hom.:

204838

Cov.:

AF XY:

0.579

AC XY:

356520

AN XY:

615540

show subpopulations

African (AFR)

AF:

0.850

AC:

24036

AN:

28284

American (AMR)

AF:

0.505

AC:

22394

AN:

44374

Ashkenazi Jewish (ASJ)

AF:

0.669

AC:

16469

AN:

24602

East Asian (EAS)

AF:

0.455

AC:

17566

AN:

38590

South Asian (SAS)

AF:

0.608

AC:

49296

AN:

81068

European-Finnish (FIN)

AF:

0.555

AC:

29573

AN:

53320

Middle Eastern (MID)

AF:

0.574

AC:

3046

AN:

5310

European-Non Finnish (NFE)

AF:

0.574

AC:

507178

AN:

884304

Other (OTH)

AF:

0.591

AC:

30779

AN:

52046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

14257

28513

42770

57026

71283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12660

25320

37980

50640

63300

<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:

0.652

AC:

99147

AN:

152090

Hom.:

33607

Cov.:

AF XY:

0.647

AC XY:

48113

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.849

AC:

35279

AN:

41534

American (AMR)

AF:

0.566

AC:

8645

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.646

AC:

2239

AN:

3468

East Asian (EAS)

AF:

0.469

AC:

2421

AN:

5164

South Asian (SAS)

AF:

0.620

AC:

2990

AN:

4822

European-Finnish (FIN)

AF:

0.556

AC:

5868

AN:

10554

Middle Eastern (MID)

AF:

0.599

AC:

176

AN:

294

European-Non Finnish (NFE)

AF:

0.583

AC:

39590

AN:

67964

Other (OTH)

AF:

0.631

AC:

1331

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1671

3342

5012

6683

8354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

782

1564

2346

3128

3910

<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:

0.611

Hom.:

88084

Bravo

AF:

0.659

Asia WGS

AF:

0.588

AC:

2047

AN:

3478

EpiCase

AF:

0.583

EpiControl

AF:

0.587

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 29, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 12, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 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. -

Congenital myasthenic syndrome 12

Benign:3

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. -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.69

CADD

Benign

9.3

(source)

DANN

Benign

0.89

PhyloP100

2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0050

dbscSNV1_RF

Benign

0.13

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