Variant rs3815076 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_138387.4(G6PC3):c.381G>A(p.Thr127=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,613,860 control chromosomes in the GnomAD database, including 22,726 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 2707 hom., cov: 32)

Exomes 𝑓: 0.11 ( 20019 hom. )

Consequence

G6PC3
NM_138387.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -5.41

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 17-44074735-G-A is Benign according to our data. Variant chr17-44074735-G-A is described in ClinVar as [Benign]. Clinvar id is 262366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
G6PC3	NM_138387.4 linkuse as main transcript	c.381G>A	p.Thr127=	synonymous_variant	3/6	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.381G>A	p.Thr127=	synonymous_variant	3/6	1	NM_138387.4	ENSP00000269097	P1

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20442

AN:

152038

Hom.:

2697

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.0857

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.727

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0709

Gnomad OTH

AF:

0.128

GnomAD3 exomes

AF:

0.189

AC:

47566

AN:

251064

Hom.:

9079

AF XY:

0.178

AC XY:

24182

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.395

Gnomad ASJ exome

AF:

0.128

Gnomad EAS exome

AF:

0.723

Gnomad SAS exome

AF:

0.192

Gnomad FIN exome

AF:

0.133

Gnomad NFE exome

AF:

0.0705

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.110

AC:

160228

AN:

1461704

Hom.:

20019

Cov.:

AF XY:

0.111

AC XY:

80722

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.380

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.723

Gnomad4 SAS exome

AF:

0.185

Gnomad4 FIN exome

AF:

0.131

Gnomad4 NFE exome

AF:

0.0683

Gnomad4 OTH exome

AF:

0.136

GnomAD4 genome

AF:

0.135

AC:

20473

AN:

152156

Hom.:

2707

Cov.:

AF XY:

0.145

AC XY:

10750

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.108

Gnomad4 AMR

AF:

0.280

Gnomad4 ASJ

AF:

0.129

Gnomad4 EAS

AF:

0.727

Gnomad4 SAS

AF:

0.201

Gnomad4 FIN

AF:

0.130

Gnomad4 NFE

AF:

0.0709

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.0922

Hom.:

1696

Bravo

AF:

0.148

Asia WGS

AF:

0.419

AC:

1452

AN:

3478

EpiCase

AF:

0.0720

EpiControl

AF:

0.0775

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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

-0.68

CADD

Benign

0.51

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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