rs116797100

Variant names:

• chr17-42904082-C-T
• rs116797100
• NM_000151.4:c.340+42C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-42904082-C-T
• chr17-42904082-C-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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: G2P, Myriad Women’s Health, Labcorp Genetics (formerly Invitae)
• glycogen storage disease I

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000151.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G6PC1	NM_000151.4	MANE Select	c.340+42C>T		intron	N/A	NP_000142.2	P35575-1
	G6PC1	NM_001270397.2		c.340+42C>T		intron	N/A	NP_001257326.1	P35575-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G6PC1	ENST00000253801.7	TSL:1 MANE Select	c.340+42C>T		intron	N/A	ENSP00000253801.1	P35575-1
	G6PC1	ENST00000887113.1		c.337+42C>T		intron	N/A	ENSP00000557172.1
	G6PC1	ENST00000887112.1		c.340+42C>T		intron	N/A	ENSP00000557171.1

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

GnomAD2 exomes AF: 0.00549 AC: 1379 AN: 251074 AF XY: 0.00420

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 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

African (AFR) AF: 0.0646 AC: 1772 AN: 27422

American (AMR) AF: 0.00508 AC: 225 AN: 44316

Ashkenazi Jewish (ASJ) AF: 0.00976 AC: 237 AN: 24274

East Asian (EAS) AF: 0.00 AC: 0 AN: 38256

South Asian (SAS) AF: 0.0000748 AC: 6 AN: 80254

European-Finnish (FIN) AF: 0.000169 AC: 9 AN: 53264

Middle Eastern (MID) AF: 0.00505 AC: 26 AN: 5150

European-Non Finnish (NFE) AF: 0.000428 AC: 358 AN: 837120

Other (OTH) AF: 0.00634 AC: 320 AN: 50436

GnomAD4 genome AF: 0.0179 AC: 2729 AN: 152232 Hom.: 75 Cov.: 31 AF XY: 0.0175 AC XY: 1304 AN XY: 74428

African (AFR) AF: 0.0601 AC: 2496 AN: 41538

American (AMR) AF: 0.00837 AC: 128 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00835 AC: 29 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10598

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 68020

Other (OTH) AF: 0.0142 AC: 30 AN: 2110

Alfa AF: 0.00905 Hom.: 12

Bravo AF: 0.0204

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Glycogen storage disease due to glucose-6-phosphatase deficiency type IA (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.16
DANN	Benign	0.71
PhyloP100		-0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs116797100; hg19: chr17-41056099;