rs1801015

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000175.5(GPI):c.489A>G(p.Gly163Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 1,613,160 control chromosomes in the GnomAD database, including 9,609 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2932 hom., cov: 30)

Exomes 𝑓: 0.080 ( 6677 hom. )

Consequence

GPI
NM_000175.5 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.807

Variant links:

Genes affected

GPI (HGNC:4458): (glucose-6-phosphate isomerase) This gene encodes a member of the glucose phosphate isomerase protein family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. In the cytoplasm, the gene product functions as a glycolytic enzyme (glucose-6-phosphate isomerase) that interconverts glucose-6-phosphate and fructose-6-phosphate. Extracellularly, the encoded protein (also referred to as neuroleukin) functions as a neurotrophic factor that promotes survival of skeletal motor neurons and sensory neurons, and as a lymphokine that induces immunoglobulin secretion. The encoded protein is also referred to as autocrine motility factor based on an additional function as a tumor-secreted cytokine and angiogenic factor. Defects in this gene are the cause of nonspherocytic hemolytic anemia and a severe enzyme deficiency can be associated with hydrops fetalis, immediate neonatal death and neurological impairment. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]

GPI links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 19-34377737-A-G is Benign according to our data. Variant chr19-34377737-A-G is described in ClinVar as [Benign]. Clinvar id is 255472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-34377737-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.807 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPI	NM_000175.5 link	c.489A>G	p.Gly163Gly	splice_region_variant, synonymous_variant	Exon 6 of 18	ENST00000356487.11	NP_000166.2	P06744-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPI	ENST00000356487.11 link	c.489A>G	p.Gly163Gly	splice_region_variant, synonymous_variant	Exon 6 of 18	1	NM_000175.5	ENSP00000348877.3		P06744-1

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23285

AN:

151678

Hom.:

2910

Cov.:

show subpopulations

Gnomad AFR

AF:

0.341

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.0927

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.0859

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0622

Gnomad OTH

AF:

0.118

GnomAD3 exomes

AF:

0.108

AC:

27032

AN:

251446

Hom.:

2217

AF XY:

0.103

AC XY:

13978

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.341

Gnomad AMR exome

AF:

0.0835

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.202

Gnomad SAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.0821

Gnomad NFE exome

AF:

0.0627

Gnomad OTH exome

AF:

0.0893

GnomAD4 exome

AF:

0.0796

AC:

116352

AN:

1461364

Hom.:

6677

Cov.:

AF XY:

0.0803

AC XY:

58343

AN XY:

727010

show subpopulations

Gnomad4 AFR exome

AF:

0.350

Gnomad4 AMR exome

AF:

0.0846

Gnomad4 ASJ exome

AF:

0.0992

Gnomad4 EAS exome

AF:

0.166

Gnomad4 SAS exome

AF:

0.142

Gnomad4 FIN exome

AF:

0.0881

Gnomad4 NFE exome

AF:

0.0610

Gnomad4 OTH exome

AF:

0.105

GnomAD4 genome

AF:

0.154

AC:

23349

AN:

151796

Hom.:

2932

Cov.:

AF XY:

0.155

AC XY:

11532

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.342

Gnomad4 AMR

AF:

0.105

Gnomad4 ASJ

AF:

0.0927

Gnomad4 EAS

AF:

0.197

Gnomad4 SAS

AF:

0.156

Gnomad4 FIN

AF:

0.0859

Gnomad4 NFE

AF:

0.0622

Gnomad4 OTH

AF:

0.120

Alfa

AF:

0.0900

Hom.:

749

Bravo

AF:

0.160

Asia WGS

AF:

0.227

AC:

791

AN:

3478

EpiCase

AF:

0.0646

EpiControl

AF:

0.0656

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hemolytic anemia due to glucophosphate isomerase deficiency

Benign:2

Nov 26, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 04, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

7.0

DANN

Benign

0.61

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

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