2-69320787-C-CA

Position:

• chr2-69320787-C-CA

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_001244710.2(GFPT1):​c.*5401_*5402insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 123,174 control chromosomes in the GnomAD database, including 29 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (29 hom., cov: 32)
  • Exomes 𝑓: 0.081 (0 hom.)
• Consequence: GFPT1 NM_001244710.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 1.09

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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0165 (2027/123088) while in subpopulation EAS AF= 0.0456 (191/4192). AF 95% confidence interval is 0.0403. There are 29 homozygotes in gnomad4. There are 939 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFPT1	NM_001244710.2	c.*5401_*5402insT		3_prime_UTR_variant	20/20	ENST00000357308.9
GFPT1	NM_002056.4	c.*5401_*5402insT		3_prime_UTR_variant	19/19
GFPT1	XM_017003801.2	c.*5401_*5402insT		3_prime_UTR_variant	20/20
GFPT1	XM_017003802.3	c.*5401_*5402insT		3_prime_UTR_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFPT1	ENST00000357308.9	c.*5401_*5402insT		3_prime_UTR_variant	20/20	5	NM_001244710.2
GFPT1	ENST00000361060.5	c.*5401_*5402insT		3_prime_UTR_variant	19/19	1		P1

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2030 AN: 123072 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.0415

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00644

Gnomad ASJ AF: 0.00325

Gnomad EAS AF: 0.0454

Gnomad SAS AF: 0.0393

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.00388

Gnomad NFE AF: 0.00327

Gnomad OTH AF: 0.0128

GnomAD4 exome AF: 0.0814 AC: 7 AN: 86 Hom.: 0 Cov.: 0 AF XY: 0.0758 AC XY: 5 AN XY: 66

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0811

GnomAD4 genome AF: 0.0165 AC: 2027 AN: 123088 Hom.: 29 Cov.: 32 AF XY: 0.0161 AC XY: 939 AN XY: 58498

Gnomad4 AFR AF: 0.0414

Gnomad4 AMR AF: 0.00643

Gnomad4 ASJ AF: 0.00325

Gnomad4 EAS AF: 0.0456

Gnomad4 SAS AF: 0.0384

Gnomad4 FIN AF: 0.00207

Gnomad4 NFE AF: 0.00327

Gnomad4 OTH AF: 0.0127

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital Myasthenic Syndrome, Recessive Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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: rs879750913; hg19: chr2-69547919;