chr17-42904082-C-T

Position:

• chr17-42904082-C-T

Variant summary

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

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.163

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 -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	Protein	UniProt
G6PC1	NM_000151.4	c.340+42C>T		intron_variant		ENST00000253801.7	NP_000142.2
G6PC1	NM_001270397.2	c.340+42C>T		intron_variant			NP_001257326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
G6PC1	ENST00000253801.7	c.340+42C>T		intron_variant		1	NM_000151.4	ENSP00000253801	P1
G6PC1	ENST00000585489.1	c.340+42C>T		intron_variant		5		ENSP00000466202
G6PC1	ENST00000592383.5	c.340+42C>T		intron_variant		2		ENSP00000465958
G6PC1	ENST00000588481.1	n.447C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2723 AN: 152114 Hom.: 75 Cov.: 31

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.: 33 AF XY: 0.00420 AC XY: 570 AN XY: 135710

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.: 72 Cov.: 16 AF XY: 0.00225 AC XY: 1331 AN XY: 591412

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.: 75 Cov.: 31 AF XY: 0.0175 AC XY: 1304 AN XY: 74428

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.: 5

Bravo AF: 0.0204

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

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

Other links and lift over

dbSNP: rs116797100; hg19: chr17-41056099;