2-69320104-G-C

Position:

• chr2-69320104-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001244710.2(GFPT1):​c.*6085C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 152,056 control chromosomes in the GnomAD database, including 34,361 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (34359 hom., cov: 32)
  • Exomes 𝑓: 0.67 (2 hom.)
• Consequence: GFPT1 NM_001244710.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.810

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 2-69320104-G-C is Benign according to our data. Variant chr2-69320104-G-C is described in ClinVar as [Benign]. Clinvar id is 336784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GFPT1	NM_001244710.2	c.*6085C>G		3_prime_UTR_variant	20/20	ENST00000357308.9	NP_001231639.1
GFPT1	NM_002056.4	c.*6085C>G		3_prime_UTR_variant	19/19		NP_002047.2
GFPT1	XM_017003801.2	c.*6085C>G		3_prime_UTR_variant	20/20		XP_016859290.1
GFPT1	XM_017003802.3	c.*6085C>G		3_prime_UTR_variant	19/19		XP_016859291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GFPT1	ENST00000357308	c.*6085C>G		3_prime_UTR_variant	20/20	5	NM_001244710.2	ENSP00000349860.4
GFPT1	ENST00000361060	c.*6085C>G		3_prime_UTR_variant	19/19	1		ENSP00000354347.4

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99955 AN: 151932 Hom.: 34317 Cov.: 32

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.629

GnomAD4 exome AF: 0.667 AC: 4 AN: 6 Hom.: 2 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 AFR exome AF: 1.00

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.658 AC: 100052 AN: 152050 Hom.: 34359 Cov.: 32 AF XY: 0.653 AC XY: 48513 AN XY: 74306

Gnomad4 AFR AF: 0.870

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.634

Alfa AF: 0.624 Hom.: 3628

Bravo AF: 0.666

Asia WGS AF: 0.593 AC: 2065 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Congenital myasthenic syndrome 12 Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.54
DANN	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97

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: rs7642; hg19: chr2-69547236;