rs2593595

chr17-42904228-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000151.4(G6PC1):c.340+188A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 602,622 control chromosomes in the GnomAD database, including 32,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (17381 hom., cov: 31)
  • Exomes 𝑓: 0.23 (15308 hom.)
• Consequence: G6PC1 NM_000151.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.871

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-42904228-A-G is Benign according to our data. Variant chr17-42904228-A-G is described in ClinVar as [Benign]. Clinvar id is 1238046.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
G6PC1	NM_000151.4	c.340+188A>G		intron_variant		ENST00000253801.7
G6PC1	NM_001270397.2	c.340+188A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
G6PC1	ENST00000253801.7	c.340+188A>G		intron_variant		1	NM_000151.4	P1
G6PC1	ENST00000585489.1	c.340+188A>G		intron_variant		5
G6PC1	ENST00000592383.5	c.340+188A>G		intron_variant		2
G6PC1	ENST00000588481.1	n.593A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58158 AN: 151984 Hom.: 17314 Cov.: 31

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.341

GnomAD4 exome AF: 0.230 AC: 103502 AN: 450520 Hom.: 15308 Cov.: 4 AF XY: 0.232 AC XY: 56358 AN XY: 242578

Gnomad4 AFR exome AF: 0.836

Gnomad4 AMR exome AF: 0.280

Gnomad4 ASJ exome AF: 0.216

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.309

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.259

GnomAD4 genome AF: 0.383 AC: 58286 AN: 152102 Hom.: 17381 Cov.: 31 AF XY: 0.381 AC XY: 28304 AN XY: 74354

Gnomad4 AFR AF: 0.839

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.337

Alfa AF: 0.219 Hom.: 11049

Bravo AF: 0.408

Asia WGS AF: 0.251 AC: 874 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.43
Dann	Benign	0.64

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: rs2593595; hg19: chr17-41056245;