rs144566433

Positions:

• chr2-69356552-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001244710.2(GFPT1):​c.549T>C​(p.Gly183Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00043 in 1,612,300 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00024 (3 hom.)
• Consequence: GFPT1 NM_001244710.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.04

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 2-69356552-A-G is Benign according to our data. Variant chr2-69356552-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 435322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.04 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00227 (345/152254) while in subpopulation AFR AF= 0.00775 (322/41562). AF 95% confidence interval is 0.00705. There are 1 homozygotes in gnomad4. There are 151 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GFPT1	NM_001244710.2	c.549T>C	p.Gly183Gly	synonymous_variant	7/20	ENST00000357308.9	NP_001231639.1
GFPT1	NM_002056.4	c.549T>C	p.Gly183Gly	synonymous_variant	7/19		NP_002047.2
GFPT1	XM_017003801.2	c.624T>C	p.Gly208Gly	synonymous_variant	7/20		XP_016859290.1
GFPT1	XM_017003802.3	c.624T>C	p.Gly208Gly	synonymous_variant	7/19		XP_016859291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GFPT1	ENST00000357308.9	c.549T>C	p.Gly183Gly	synonymous_variant	7/20	5	NM_001244710.2	ENSP00000349860.4
GFPT1	ENST00000361060.5	c.549T>C	p.Gly183Gly	synonymous_variant	7/19	1		ENSP00000354347.4
GFPT1	ENST00000674507.1	c.549T>C	p.Gly183Gly	synonymous_variant	7/18			ENSP00000501332.1
GFPT1	ENST00000674438.1	c.333T>C	p.Gly111Gly	synonymous_variant	5/17			ENSP00000501469.1

Frequencies

GnomAD3 genomes AF: 0.00226 AC: 344 AN: 152134 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00775

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.000493 AC: 124 AN: 251330 Hom.: 1 AF XY: 0.000383 AC XY: 52 AN XY: 135848

Gnomad AFR exome AF: 0.00683

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000239 AC: 349 AN: 1460046 Hom.: 3 Cov.: 29 AF XY: 0.000206 AC XY: 150 AN XY: 726510

Gnomad4 AFR exome AF: 0.00828

Gnomad4 AMR exome AF: 0.000559

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000720

Gnomad4 OTH exome AF: 0.000530

GnomAD4 genome AF: 0.00227 AC: 345 AN: 152254 Hom.: 1 Cov.: 33 AF XY: 0.00203 AC XY: 151 AN XY: 74448

Gnomad4 AFR AF: 0.00775

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.00123 Hom.: 1

Bravo AF: 0.00262

Asia WGS AF: 0.000866 AC: 3 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

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 11, 2016

- -

GFPT1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 02, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 12, 2021

- -

Congenital myasthenic syndrome 12 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.6
DANN	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs144566433; hg19: chr2-69583684;