Variant chr17-44070837-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_138387.4(G6PC3):c.-129C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 1,062,146 control chromosomes in the GnomAD database, including 131,665 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 13668 hom., cov: 28)

Exomes 𝑓: 0.50 ( 117997 hom. )

Consequence

G6PC3
NM_138387.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.02

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 17-44070837-C-T is Benign according to our data. Variant chr17-44070837-C-T is described in ClinVar as [Benign]. Clinvar id is 323459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
G6PC3	NM_138387.4 linkuse as main transcript	c.-129C>T		5_prime_UTR_variant	1/6	ENST00000269097.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
G6PC3	ENST00000269097.9 linkuse as main transcript	c.-129C>T		5_prime_UTR_variant	1/6	1	NM_138387.4	P1

Frequencies

GnomAD3 genomes

AF:

0.382

AC:

57427

AN:

150486

Hom.:

13667

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.540

Gnomad AMR

AF:

0.387

Gnomad ASJ

AF:

0.508

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.552

Gnomad FIN

AF:

0.405

Gnomad MID

AF:

0.564

Gnomad NFE

AF:

0.537

Gnomad OTH

AF:

0.455

GnomAD3 exomes

AF:

0.452

AC:

57757

AN:

127866

Hom.:

14239

AF XY:

0.469

AC XY:

32773

AN XY:

69896

show subpopulations

Gnomad AFR exome

AF:

0.0930

Gnomad AMR exome

AF:

0.364

Gnomad ASJ exome

AF:

0.513

Gnomad EAS exome

AF:

0.206

Gnomad SAS exome

AF:

0.549

Gnomad FIN exome

AF:

0.412

Gnomad NFE exome

AF:

0.542

Gnomad OTH exome

AF:

0.498

GnomAD4 exome

AF:

0.498

AC:

453524

AN:

911548

Hom.:

117997

Cov.:

AF XY:

0.503

AC XY:

234574

AN XY:

466576

show subpopulations

Gnomad4 AFR exome

AF:

0.0906

Gnomad4 AMR exome

AF:

0.372

Gnomad4 ASJ exome

AF:

0.506

Gnomad4 EAS exome

AF:

0.199

Gnomad4 SAS exome

AF:

0.547

Gnomad4 FIN exome

AF:

0.422

Gnomad4 NFE exome

AF:

0.534

Gnomad4 OTH exome

AF:

0.470

GnomAD4 genome

AF:

0.381

AC:

57420

AN:

150598

Hom.:

13668

Cov.:

AF XY:

0.377

AC XY:

27754

AN XY:

73578

show subpopulations

Gnomad4 AFR

AF:

0.100

Gnomad4 AMR

AF:

0.386

Gnomad4 ASJ

AF:

0.508

Gnomad4 EAS

AF:

0.192

Gnomad4 SAS

AF:

0.552

Gnomad4 FIN

AF:

0.405

Gnomad4 NFE

AF:

0.537

Gnomad4 OTH

AF:

0.457

Alfa

AF:

0.385

Hom.:

1996

Bravo

AF:

0.365

Asia WGS

AF:

0.382

AC:

1328

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

- -

Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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

-0.92

CADD

Benign

1.1

DANN

Benign

0.65

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

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