rs113416399

Positions:

chr17-44076045-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_138387.4(G6PC3):c.*2T>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 0.0103 in 1,612,470 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 4 hom., cov: 32)

Exomes 𝑓: 0.011 ( 90 hom. )

Consequence

G6PC3
NM_138387.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.440

Variant links:

Genes affected

G6PC3 (HGNC:24861): (glucose-6-phosphatase catalytic subunit 3) This gene encodes the catalytic subunit of glucose-6-phosphatase (G6Pase). G6Pase is located in the endoplasmic reticulum (ER) and catalyzes the hydrolysis of glucose-6-phosphate to glucose and phosphate in the last step of the gluconeogenic and glycogenolytic pathways. Mutations in this gene result in autosomal recessive severe congenital neutropenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

G6PC3 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=-0.76).

BP6

Variant 17-44076045-T-C is Benign according to our data. Variant chr17-44076045-T-C is described in ClinVar as [Benign]. Clinvar id is 211056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00691 (1052/152312) while in subpopulation NFE AF= 0.0127 (863/68022). AF 95% confidence interval is 0.012. There are 4 homozygotes in gnomad4. There are 458 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
G6PC3	NM_138387.4 linkuse as main transcript	c.*2T>C		3_prime_UTR_variant	6/6	ENST00000269097.9	NP_612396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
G6PC3	ENST00000269097.9 linkuse as main transcript	c.*2T>C		3_prime_UTR_variant	6/6	1	NM_138387.4	ENSP00000269097	P1

Frequencies

GnomAD3 genomes

AF:

0.00691

AC:

1052

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00229

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00643

AC:

1611

AN:

250448

Hom.:

AF XY:

0.00630

AC XY:

853

AN XY:

135474

show subpopulations

Gnomad AFR exome

AF:

0.00228

Gnomad AMR exome

AF:

0.00286

Gnomad ASJ exome

AF:

0.000893

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00212

Gnomad FIN exome

AF:

0.00179

Gnomad NFE exome

AF:

0.0115

Gnomad OTH exome

AF:

0.00848

GnomAD4 exome

AF:

0.0106

AC:

15485

AN:

1460158

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

7613

AN XY:

726528

show subpopulations

Gnomad4 AFR exome

AF:

0.00206

Gnomad4 AMR exome

AF:

0.00304

Gnomad4 ASJ exome

AF:

0.000689

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00250

Gnomad4 FIN exome

AF:

0.00234

Gnomad4 NFE exome

AF:

0.0129

Gnomad4 OTH exome

AF:

0.00924

GnomAD4 genome

AF:

0.00691

AC:

1052

AN:

152312

Hom.:

Cov.:

AF XY:

0.00615

AC XY:

458

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00229

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.0127

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00956

Hom.:

Bravo

AF:

0.00703

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0112

EpiControl

AF:

0.00948

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 19, 2016

- -

G6PC3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 16, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

G6PC3: BS1, BS2 -

Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.0

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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