Variant chr17-42904082-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000151.4(G6PC1):c.340+42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00433 in 1,312,724 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 75 hom., cov: 31)

Exomes 𝑓: 0.0025 ( 72 hom. )

Consequence

G6PC1
NM_000151.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.163

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 links:

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=-0.88).

BP6

Variant 17-42904082-C-T is Benign according to our data. Variant chr17-42904082-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 255351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
G6PC1	NM_000151.4 linkuse as main transcript	c.340+42C>T		intron_variant		ENST00000253801.7
G6PC1	NM_001270397.2 linkuse as main transcript	c.340+42C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
G6PC1	ENST00000253801.7 linkuse as main transcript	c.340+42C>T	intron_variant		1	NM_000151.4	P1	P35575-1
G6PC1	ENST00000585489.1 linkuse as main transcript	c.340+42C>T	intron_variant		5
G6PC1	ENST00000592383.5 linkuse as main transcript	c.340+42C>T	intron_variant		2			P35575-2
G6PC1	ENST00000588481.1 linkuse as main transcript	n.447C>T	non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0179

AC:

2723

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0601

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00838

Gnomad ASJ

AF:

0.00835

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.00549

AC:

1379

AN:

251074

Hom.:

AF XY:

0.00420

AC XY:

570

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.0632

Gnomad AMR exome

AF:

0.00437

Gnomad ASJ exome

AF:

0.0111

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000564

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00254

AC:

2953

AN:

1160492

Hom.:

Cov.:

AF XY:

0.00225

AC XY:

1331

AN XY:

591412

show subpopulations

Gnomad4 AFR exome

AF:

0.0646

Gnomad4 AMR exome

AF:

0.00508

Gnomad4 ASJ exome

AF:

0.00976

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000748

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.000428

Gnomad4 OTH exome

AF:

0.00634

GnomAD4 genome

AF:

0.0179

AC:

2729

AN:

152232

Hom.:

Cov.:

AF XY:

0.0175

AC XY:

1304

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0601

Gnomad4 AMR

AF:

0.00837

Gnomad4 ASJ

AF:

0.00835

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00936

Hom.:

Bravo

AF:

0.0204

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 02, 2019	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Apr 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.16

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over