NM_138387.4:c.879G>T

Variant names:

• chr17-44075881-G-T
• rs780718603
• NM_138387.4:c.879G>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_138387.4(G6PC3):​c.879G>T​(p.Leu293Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L293L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: G6PC3 NM_138387.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.363
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-44075881-G-T is Benign according to our data. Variant chr17-44075881-G-T is described in CliVar as Likely_benign. Clinvar id is 3852356.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-44075881-G-T is described in CliVar as Likely_benign. Clinvar id is 3852356.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-44075881-G-T is described in CliVar as Likely_benign. Clinvar id is 3852356.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-44075881-G-T is described in CliVar as Likely_benign. Clinvar id is 3852356.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-44075881-G-T is described in CliVar as Likely_benign. Clinvar id is 3852356.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-44075881-G-T is described in CliVar as Likely_benign. Clinvar id is 3852356.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-44075881-G-T is described in CliVar as Likely_benign. Clinvar id is 3852356.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-44075881-G-T is described in CliVar as Likely_benign. Clinvar id is 3852356.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-44075881-G-T is described in CliVar as Likely_benign. Clinvar id is 3852356.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-44075881-G-T is described in CliVar as Likely_benign. Clinvar id is 3852356.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-44075881-G-T is described in CliVar as Likely_benign. Clinvar id is 3852356.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-44075881-G-T is described in CliVar as Likely_benign. Clinvar id is 3852356.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-44075881-G-T is described in CliVar as Likely_benign. Clinvar id is 3852356.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-44075881-G-T is described in CliVar as Likely_benign. Clinvar id is 3852356.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.363 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
G6PC3	NM_138387.4	c.879G>T	p.Leu293Leu	synonymous_variant	Exon 6 of 6	ENST00000269097.9	NP_612396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
G6PC3	ENST00000269097.9	c.879G>T	p.Leu293Leu	synonymous_variant	Exon 6 of 6	1	NM_138387.4	ENSP00000269097.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460290 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726530

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111982

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Benign:1

Jan 27, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.60
DANN	Benign	0.70
PhyloP100		-0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs780718603; hg19: chr17-42153249;