chr17-44074735-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_138387.4(G6PC3):c.381G>A(p.Thr127Thr) 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:7

Conservation

PhyloP100: -5.41

Publications

23 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive severe congenital neutropenia due to G6PC3 deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

G6PC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
G6PC3	NM_138387.4 link	c.381G>A	p.Thr127Thr	synonymous_variant	Exon 3 of 6	ENST00000269097.9	NP_612396.1	Q9BUM1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
G6PC3	ENST00000269097.9 link	c.381G>A	p.Thr127Thr	synonymous_variant	Exon 3 of 6	1	NM_138387.4	ENSP00000269097.3		Q9BUM1

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

GnomAD2 exomes

AF:

0.189

AC:

47566

AN:

251064

AF XY:

0.178

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 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

African (AFR)

AF:

0.106

AC:

3535

AN:

33478

American (AMR)

AF:

0.380

AC:

16960

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

3313

AN:

26132

East Asian (EAS)

AF:

0.723

AC:

28684

AN:

39688

South Asian (SAS)

AF:

0.185

AC:

15999

AN:

86248

European-Finnish (FIN)

AF:

0.131

AC:

7010

AN:

53390

Middle Eastern (MID)

AF:

0.108

AC:

621

AN:

5768

European-Non Finnish (NFE)

AF:

0.0683

AC:

75910

AN:

1111924

Other (OTH)

AF:

0.136

AC:

8196

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

7239

14477

21716

28954

36193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3352

6704

10056

13408

16760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.135

AC:

20473

AN:

152156

Hom.:

2707

Cov.:

AF XY:

0.145

AC XY:

10750

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.108

AC:

4468

AN:

41536

American (AMR)

AF:

0.280

AC:

4272

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

447

AN:

3466

East Asian (EAS)

AF:

0.727

AC:

3747

AN:

5154

South Asian (SAS)

AF:

0.201

AC:

969

AN:

4824

European-Finnish (FIN)

AF:

0.130

AC:

1376

AN:

10592

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0709

AC:

4818

AN:

67994

Other (OTH)

AF:

0.131

AC:

276

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

787

1573

2360

3146

3933

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.102

Hom.:

3424

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:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Sep 04, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 22, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 -

Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.78

PhyloP100

-5.4

PromoterAI

-0.049

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over