G6PC3 p.Leu293Leu

Variant names:

• chr17-44075878-G-G
• NM_138387.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr17-44075879--
• chr17-44075879-C-T
• chr17-44075881-G-T
• chr17-44075881-G-C
• chr17-44075881-G-A
• chr17-44075879-CTG-TTA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138387.4(G6PC3):​c. variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: G6PC3 NM_138387.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• 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, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138387.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G6PC3	NM_138387.4	MANE Select	c.		intron	N/A	NP_612396.1	Q9BUM1
	G6PC3	NM_001384165.1		c.		intron	N/A	NP_001371094.1	A0A8Q3SIG5
	G6PC3	NM_001384166.1		c.		intron	N/A	NP_001371095.1	A0A8Q3SIG5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G6PC3	ENST00000696393.1		c.		intron	N/A	ENSP00000512603.1	A0A8Q3WL73
	G6PC3	ENST00000696405.1		c.		intron	N/A	ENSP00000512607.1	A0A8Q3WME5
	G6PC3	ENST00000696392.1		n.		intron	N/A	ENSP00000512602.1	A0A8Q3WL73

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-42153246;