rs78952091

Positions:

chr2-69354499-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001244710.2(GFPT1):c.675C>T(p.Leu225=) 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 129153.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-69354499-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein
GFPT1	NM_001244710.2 linkuse as main transcript	c.675C>T	p.Leu225=	synonymous_variant	8/20	ENST00000357308.9	NP_001231639.1
GFPT1	NM_002056.4 linkuse as main transcript	c.675C>T	p.Leu225=	synonymous_variant	8/19		NP_002047.2
GFPT1	XM_017003801.2 linkuse as main transcript	c.750C>T	p.Leu250=	synonymous_variant	8/20		XP_016859290.1
GFPT1	XM_017003802.3 linkuse as main transcript	c.750C>T	p.Leu250=	synonymous_variant	8/19		XP_016859291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GFPT1	ENST00000357308.9 linkuse as main transcript	c.675C>T	p.Leu225=	synonymous_variant	8/20	5	NM_001244710.2	ENSP00000349860		Q06210-1
GFPT1	ENST00000361060.5 linkuse as main transcript	c.675C>T	p.Leu225=	synonymous_variant	8/19	1		ENSP00000354347	P1	Q06210-2
GFPT1	ENST00000674507.1 linkuse as main transcript	c.675C>T	p.Leu225=	synonymous_variant	8/18			ENSP00000501332
GFPT1	ENST00000674438.1 linkuse as main transcript	c.459C>T	p.Leu153=	synonymous_variant	6/17			ENSP00000501469

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

GnomAD3 exomes

AF:

0.0285

AC:

7152

AN:

251134

Hom.:

488

AF XY:

0.0306

AC XY:

4159

AN XY:

135706

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 SAS exome

AF:

0.0997

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

Gnomad4 AFR exome

AF:

0.0135

Gnomad4 AMR exome

AF:

0.00186

Gnomad4 ASJ exome

AF:

0.00505

Gnomad4 EAS exome

AF:

0.188

Gnomad4 SAS exome

AF:

0.0937

Gnomad4 FIN exome

AF:

0.000731

Gnomad4 NFE exome

AF:

0.00198

Gnomad4 OTH exome

AF:

0.0215

GnomAD4 genome

AF:

0.0147

AC:

2234

AN:

152210

Hom.:

128

Cov.:

AF XY:

0.0169

AC XY:

1259

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0127

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.184

Gnomad4 SAS

AF:

0.0971

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.00232

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.00522

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

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 18, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Congenital myasthenic syndrome 12

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

1.5

DANN

Benign

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over