2-69320104-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.810
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
GFPT1NM_001244710.2 linkuse as main transcriptc.*6085C>G 3_prime_UTR_variant 20/20 ENST00000357308.9 NP_001231639.1 Q06210-1
GFPT1NM_002056.4 linkuse as main transcriptc.*6085C>G 3_prime_UTR_variant 19/19 NP_002047.2 Q06210-2
GFPT1XM_017003801.2 linkuse as main transcriptc.*6085C>G 3_prime_UTR_variant 20/20 XP_016859290.1
GFPT1XM_017003802.3 linkuse as main transcriptc.*6085C>G 3_prime_UTR_variant 19/19 XP_016859291.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GFPT1ENST00000357308 linkuse as main transcriptc.*6085C>G 3_prime_UTR_variant 20/205 NM_001244710.2 ENSP00000349860.4 Q06210-1
GFPT1ENST00000361060.5 linkuse as main transcriptc.*6085C>G 3_prime_UTR_variant 19/191 ENSP00000354347.4 Q06210-2

Frequencies

GnomAD3 genomes
AF:
0.658
AC:
99955
AN:
151932
Hom.:
34317
Cov.:
32
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Congenital myasthenic syndrome 12 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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

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

Other links and lift over

dbSNP: rs7642; hg19: chr2-69547236; API