17-42911449-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000151.4(G6PC1):c.*23T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 1,613,692 control chromosomes in the GnomAD database, including 467,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 40789 hom., cov: 31)

Exomes 𝑓: 0.76 ( 426315 hom. )

Consequence

G6PC1
NM_000151.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.696

Publications

38 publications found

Variant links:

Genes affected

G6PC1 (HGNC:4056): (glucose-6-phosphatase catalytic subunit 1) Glucose-6-phosphatase (G6Pase) is a multi-subunit integral membrane protein of the endoplasmic reticulum that is composed of a catalytic subunit and transporters for G6P, inorganic phosphate, and glucose. This gene (G6PC) is one of the three glucose-6-phosphatase catalytic-subunit-encoding genes in human: G6PC, G6PC2 and G6PC3. Glucose-6-phosphatase catalyzes the hydrolysis of D-glucose 6-phosphate to D-glucose and orthophosphate and is a key enzyme in glucose homeostasis, functioning in gluconeogenesis and glycogenolysis. Mutations in this gene cause glycogen storage disease type I (GSD1). This disease, also known as von Gierke disease, is a metabolic disorder characterized by severe hypoglycemia associated with the accumulation of glycogen and fat in the liver and kidneys.[provided by RefSeq, Feb 2011]

G6PC1 Gene-Disease associations (from GenCC):

glycogen storage disease due to glucose-6-phosphatase deficiency type IA
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Myriad Women’s Health

G6PC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 17-42911449-T-C is Benign according to our data. Variant chr17-42911449-T-C is described in CliVar as Benign. Clinvar id is 255350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
G6PC1	NM_000151.4 link	c.*23T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000253801.7	NP_000142.2	P35575-1
G6PC1	NM_001270397.2 link	c.*489T>C		3_prime_UTR_variant	Exon 5 of 5		NP_001257326.1	P35575-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
G6PC1	ENST00000253801.7 link	c.*23T>C	3_prime_UTR_variant	Exon 5 of 5	1	NM_000151.4	ENSP00000253801.1	P35575-1
G6PC1	ENST00000585489.1 link	c.*489T>C	3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000466202.1	K7ELS6
G6PC1	ENST00000592383.5 link	c.*489T>C	downstream_gene_variant		2		ENSP00000465958.1	P35575-2

Frequencies

GnomAD3 genomes

AF:

0.728

AC:

110626

AN:

151990

Hom.:

40789

Cov.:

show subpopulations

Gnomad AFR

AF:

0.688

Gnomad AMI

AF:

0.934

Gnomad AMR

AF:

0.625

Gnomad ASJ

AF:

0.779

Gnomad EAS

AF:

0.456

Gnomad SAS

AF:

0.639

Gnomad FIN

AF:

0.816

Gnomad MID

AF:

0.731

Gnomad NFE

AF:

0.783

Gnomad OTH

AF:

0.732

GnomAD2 exomes

AF:

0.708

AC:

176095

AN:

248560

AF XY:

0.714

show subpopulations

Gnomad AFR exome

AF:

0.685

Gnomad AMR exome

AF:

0.575

Gnomad ASJ exome

AF:

0.778

Gnomad EAS exome

AF:

0.449

Gnomad FIN exome

AF:

0.812

Gnomad NFE exome

AF:

0.783

Gnomad OTH exome

AF:

0.734

GnomAD4 exome

AF:

0.760

AC:

1110785

AN:

1461584

Hom.:

426315

Cov.:

AF XY:

0.758

AC XY:

551463

AN XY:

727110

show subpopulations

African (AFR)

AF:

0.687

AC:

23006

AN:

33480

American (AMR)

AF:

0.584

AC:

26116

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.776

AC:

20276

AN:

26136

East Asian (EAS)

AF:

0.446

AC:

17719

AN:

39698

South Asian (SAS)

AF:

0.654

AC:

56409

AN:

86220

European-Finnish (FIN)

AF:

0.815

AC:

43384

AN:

53254

Middle Eastern (MID)

AF:

0.719

AC:

4149

AN:

5768

European-Non Finnish (NFE)

AF:

0.787

AC:

874766

AN:

1111922

Other (OTH)

AF:

0.744

AC:

44960

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

14986

29973

44959

59946

74932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20522

41044

61566

82088

102610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.727

AC:

110656

AN:

152108

Hom.:

40789

Cov.:

AF XY:

0.721

AC XY:

53647

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.687

AC:

28521

AN:

41486

American (AMR)

AF:

0.624

AC:

9527

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.779

AC:

2706

AN:

3472

East Asian (EAS)

AF:

0.455

AC:

2352

AN:

5172

South Asian (SAS)

AF:

0.638

AC:

3071

AN:

4810

European-Finnish (FIN)

AF:

0.816

AC:

8631

AN:

10582

Middle Eastern (MID)

AF:

0.735

AC:

216

AN:

294

European-Non Finnish (NFE)

AF:

0.783

AC:

53235

AN:

67994

Other (OTH)

AF:

0.732

AC:

1545

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1495

2990

4484

5979

7474

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

838

1676

2514

3352

4190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.760

Hom.:

197803

Bravo

AF:

0.714

Asia WGS

AF:

0.560

AC:

1950

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Glycogen storage disease due to glucose-6-phosphatase deficiency type IA

Benign:4

Apr 12, 2018

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 08, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:3

Oct 19, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 29, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 33101979, 28502559) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.8

(source)

DANN

Benign

0.68

PhyloP100

-0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over