17-44074110-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_138387.4(G6PC3):c.219-50C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,315,042 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00078 (4 hom.)
• Consequence: G6PC3 NM_138387.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.631

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 17-44074110-C-G is Benign according to our data. Variant chr17-44074110-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 262365.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00352 (535/152180) while in subpopulation AFR AF= 0.0116 (482/41512). AF 95% confidence interval is 0.0108. There are 3 homozygotes in gnomad4. There are 250 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
G6PC3	NM_138387.4	c.219-50C>G		intron_variant		ENST00000269097.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
G6PC3	ENST00000269097.9	c.219-50C>G		intron_variant		1	NM_138387.4	P1

Frequencies

GnomAD3 genomes AF: 0.00352 AC: 535 AN: 152066 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00134 AC: 336 AN: 250586 Hom.: 1 AF XY: 0.00111 AC XY: 151 AN XY: 135528

Gnomad AFR exome AF: 0.0123

Gnomad AMR exome AF: 0.000578

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00118

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000496

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000777 AC: 904 AN: 1162862 Hom.: 4 Cov.: 16 AF XY: 0.000730 AC XY: 433 AN XY: 592940

Gnomad4 AFR exome AF: 0.0117

Gnomad4 AMR exome AF: 0.000654

Gnomad4 ASJ exome AF: 0.00145

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000947

Gnomad4 FIN exome AF: 0.000131

Gnomad4 NFE exome AF: 0.000442

Gnomad4 OTH exome AF: 0.00113

GnomAD4 genome AF: 0.00352 AC: 535 AN: 152180 Hom.: 3 Cov.: 32 AF XY: 0.00336 AC XY: 250 AN XY: 74398

Gnomad4 AFR AF: 0.0116

Gnomad4 AMR AF: 0.000524

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.000385 Hom.: 0

Bravo AF: 0.00415

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.049
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs148256151; hg19: chr17-42151478;