2-69338431-TAA-TA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001244710.2(GFPT1):c.1324+13del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,606,626 control chromosomes in the GnomAD database, including 18,915 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1400 hom., cov: 30)
  • Exomes 𝑓: 0.15 (17515 hom.)
• Consequence: GFPT1 NM_001244710.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.763

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 2-69338431-TA-T is Benign according to our data. Variant chr2-69338431-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 257667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-69338431-TA-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFPT1	NM_001244710.2	c.1324+13del		intron_variant		ENST00000357308.9
GFPT1	NM_002056.4	c.1270+13del		intron_variant
GFPT1	XM_017003801.2	c.1399+13del		intron_variant
GFPT1	XM_017003802.3	c.1345+13del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFPT1	ENST00000357308.9	c.1324+13del		intron_variant		5	NM_001244710.2
GFPT1	ENST00000361060.5	c.1270+13del		intron_variant		1		P1
GFPT1	ENST00000674438.1	c.1054+13del		intron_variant
GFPT1	ENST00000674507.1	c.1270+13del		intron_variant

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19434 AN: 152104 Hom.: 1400 Cov.: 30

Gnomad AFR AF: 0.0953

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.0997

Gnomad ASJ AF: 0.0969

Gnomad EAS AF: 0.0379

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.120

GnomAD3 exomes AF: 0.123 AC: 30767 AN: 250048 Hom.: 2155 AF XY: 0.127 AC XY: 17218 AN XY: 135124

Gnomad AFR exome AF: 0.0931

Gnomad AMR exome AF: 0.0676

Gnomad ASJ exome AF: 0.102

Gnomad EAS exome AF: 0.0300

Gnomad SAS exome AF: 0.132

Gnomad FIN exome AF: 0.138

Gnomad NFE exome AF: 0.156

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.150 AC: 218191 AN: 1454404 Hom.: 17515 Cov.: 27 AF XY: 0.150 AC XY: 108737 AN XY: 723904

Gnomad4 AFR exome AF: 0.0945

Gnomad4 AMR exome AF: 0.0708

Gnomad4 ASJ exome AF: 0.0987

Gnomad4 EAS exome AF: 0.0183

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.164

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.128 AC: 19438 AN: 152222 Hom.: 1400 Cov.: 30 AF XY: 0.125 AC XY: 9294 AN XY: 74426

Gnomad4 AFR AF: 0.0952

Gnomad4 AMR AF: 0.0995

Gnomad4 ASJ AF: 0.0969

Gnomad4 EAS AF: 0.0378

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.120

Alfa AF: 0.138 Hom.: 272

Bravo AF: 0.122

Asia WGS AF: 0.0890 AC: 310 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Congenital Myasthenic Syndrome, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 29, 2018

- -

Congenital myasthenic syndrome 12 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs113734896; hg19: chr2-69565563;